Three-pronged attacks by hybrid nanoassemblies involving a natural product, carbon dots, and Cu2+ for synergistic HCC therapy.

Tumor microenvironment (TME) stimuli-responsive nanoassemblies are emerging as promising drug delivery systems (DDSs), which acquire controlled release by structural transformation under exogenous stimulation. However, the design of smart stimuli-responsive nanoplatforms integrated with nanomaterials to achieve complete tumor ablation remains challenging. Therefore, it is of utmost importance to develop TME-based stimuli-responsive DDSs to enhance drug-targeted delivery and release at tumor sites. Herein, we proposed an appealing strategy to construct fluorescence-mediated TME stimulus-responsive nanoplatforms for synergistic cancer therapy by assembling photosensitizers (PSs) carbon dots (CDs), chemotherapeutic agent ursolic acid (UA), and copper ions (Cu2+). First, UA nanoparticles (UA NPs) were prepared by self-assembly of UA, then UA NPs were assembled with CDs via hydrogen bonding force to obtain UC NPs. After combining with Cu2+, the resulting particles (named UCCu2+ NPs) exhibited quenched fluorescence and photosensitization due to the aggregation of UC NPs. Upon entering the tumor tissue, the photodynamic therapy (PDT) and the fluorescence function of UCCu2+ were recovered in response to TME stimulation. The introduction of Cu2+ triggered the charge reversal of UCCu2+ NPs, thereby promoting lysosomal escape. Furthermore, Cu2+ resulted in additional chemodynamic therapy (CDT) capacity by reacting with hydrogen peroxide (H2O2) as well as by consuming glutathione (GSH) in cancer cells through a redox reaction, hence magnifying intracellular oxidative stress and enhancing the therapeutic efficacy due to reactive oxygen species (ROS) therapy. In summary, UCCu2+ NPs provided an unprecedented novel approach for improving the therapeutic efficacy through the three-pronged (chemotherapy, phototherapy, and heat-reinforced CDT) attacks to achieve synergistic therapy.

Comparative Efficacy of Local and General Anesthesia for Transcatheter Aortic Valve Implantation: A Meta-Analysis and Systematic Review.

BACKGROUND: This meta-analysis aimed to compare the potential effects of local anesthesia (LA) and general anesthesia (GA) for transcatheter aortic valve implantation (TAVI). MEASUREMENTS: All relevant studies were searched from Pubmed, EMbase, Web of Science, and the Cochrane Library (January 1, 2016, to June 1, 2021). The main outcomes of this literature meta-analysis were 30-day mortality, procedural time, new pacemaker implantation, total stay in the hospital, use of the vasoactive drug, and intra-and postoperative complications and emergencies, including conversion to open, myocardial infarction, pulmonary complication, vascular complication, renal injury/failure, stroke, transesophageal echocardiography, life-threatening/major bleeding, cardiac tamponade, and emergency PCI. Pooled risk ratio (RR) and mean difference (MD) together with a 95% confidence interval (CI) were calculated. RESULTS: A total of 17 studies, including 20938 patients, in the final analysis, fulfilled the inclusion criteria. Intra-and postoperative complications (myocardial infarction, vascular complication, renal injury/failure, stroke, and cardiac tamponade) undergoing TAVI in severe AS patients under GA do not offer a significant difference compared with LA. No differences were observed between LA and GA for new pacemaker implantation, total stay in the hospital, transesophageal echocardiography, and emergency PCI. LA has lower mortality compared with GA (RR 0.69, P = 0.600), pulmonary complications (RR 0.54, P = 0.278), life-threatening/major bleeding (RR 0.85, P = 0.855), and lower times of conversion to open (RR 0.22, P = 0.746). LA has many advantages, including a shorter procedure duration (MD=-0.38, P = 0.000) and reduction of the use of the vasoactive drug (RR 0.57, P = 0.000). CONCLUSIONS: For TAVI, both LA with or without sedation and GA are feasible and safe. LA appears a feasible alternative to GA for AS patients undergoing TAVI.

Treatment of knee osteoarthritis with six-step manipulation combined with extracorporeal shock wave / 中国骨伤

OBJECTIVE@#To observe the clinical effect of six-step manipulation combined with extracorporeal shock wave in the treatment of knee osteoarthritis.@*METHODS@#Seventy-six patients with KOA from December 2016 to June 2018 were divided into control group and treatment group, 38 in each group. The patients in the control group were treated with oral medicine combined with extracorporeal shock wave therapy, while the patients in the treatment group were treated with six-step manipulation combined with shock wave therapy. The VAS score, WOMAC score and clinical efficacy of the two groups were compared before treatment, 1 day, 1 month and 6 months after treatment.@*RESULTS@#There was no significant difference in VAS score and WOMAC score between the two groups before treatment(>0.05). VAS score and WOMAC score in treatment group were significantly lower than those in control group at 1 day, 1 month and 6 months after treatment, and the difference was statistically significant(<0.05).@*CONCLUSIONS@#Six-step manipulation combined with extracorporeal shock wave therapy can significantly alleviate pain and improve knee function in patients with knee osteoarthritis, and the clinical effect is obvious.

Walnut oil promotes healing of wounds and skin defects in rats via regulating the NF-kB pathway.

The effects of walnut oil on wound healing and skin injury repair was observed in Sprague-Dawley (SD) rats, and mechanism of action was investigated. Normal SD rats were divided into an experimental group and a control group. Each group was observed at4 time points (day [D]3, D7, D14, and D21). In both groups, a skin wound was created on the back of the rats, with the spine as the central axis. In the experimental group, the wound was covered with walnut oil, and then bandaged and fixed with sterile gauze. In the control group, the wound was bandaged with vaseline gauze. At each corresponding time point, the wound area and wound healing time of each rat were examined. Epithelial cells of the wound tissues were observed using haematoxylin and eosin staining and immunohistochemical analysis,and the numbers of inflammatory cells and capillaries were counted. A western blot method was used to detect the expression of nuclear factor (NF)-κB and epidermal growth factor (EGF) in the wound tissues of both groups. Meanwhile, enzyme-linked immunosorbent analysis (ELISA) was used to detect the expression of transforming growth factor (TGF)-ß1 and matrix metalloproteinase (MMP)-1 in rat sera. A total of 48 SD rats completed the experiment. Healing time of residual wounds in the experimental group was 10.0±3.5 days, which was significantly shorter than that in the control group (18.0±6.0 days) (p<0.05). The wound healing rates in the experimental group were 54.14 % (D3) and 91.2 3% (D7), whereas those in the control group were 22.12% (D3) and 54.84% (D7 (p<0.05).Histological examinations revealed no epithelial cells on D3, D7, D14, and D21 in both the experimental and control groups. However, the number of inflammatory cells decreased significantly and the number of capillaries increased significantly in the experimental group compared to control (p<0.05). NF-κB expression was significantly lower, EGF expression significantly higher in the in the experimental group. Conversely, ELISA showed a significant increase in the expression of TGF-ß1 and MMP-1 in rat sera in the experimental group. So we conclude that walnut oil has significant effects in promoting the healing of skin defect wounds in SD rats.

Cytotoxicity of anti-tumor herbal Marsdeniae tenacissimae extract on erythrocytes.

Marsdeniae tenacissimae extract (MTE) has been used as an adjuvant medicine for cancer therapy for a long time. Although massive studies demonstrated its considerable anti-cancer effect, there is no research on its influence on erythrocytes, which are firstly interacted with MTE in the circulation. To investigate the influence of MTE on erythrocytes, we used a flow cytometer to detect the MTE-treated alternations of morphology, calcium concentration, and reactive oxygen species (ROS) level in erythrocytes. We used hemolysis under different osmotic solutions to evaluate the fragility of erythrocytes. Data showed that MTE treatment dose-dependently increased the ratio of erythrocyte fragmentation (P<0.001) and shrinking, and elevated the forward scatter (FSC) value (P<0.001) and calcium accumulation (P<0.001). MTE induced ROS production of erythrocytes under the high glucose condition (P<0.01) and consequently caused a rise in fragility (P<0.05). These results suggest that MTE induces cytotoxicity and aging in erythrocytes in a dose-dependent manner, and presents the possibility of impairment on cancer patients' circulating erythrocytes when MTE is used as an anti-cancer adjuvant medicine.

Chronic treatment with qiliqiangxin ameliorates aortic endothelial cell dysfunction in diabetic rats.

Qiliqiangxin (QL), a traditional Chinese medicine, has been shown to be beneficial for chronic heart failure. However, whether QL can also improve endothelial cell function in diabetic rats remains unknown. Here, we investigated the effect of QL treatment on endothelial dysfunction by comparing the effect of QL to that of benazepril (Ben) in diabetic Sprague-Dawley rats for 8 weeks. Cardiac function was evaluated by echocardiography and catheterization. Assays for acetylcholine-induced, endothelium-dependent relaxation (EDR), sodium nitroprusside-induced endothelium-independent relaxation, serum nitric oxide (NO), and nitric oxide synthase (NOS) as well as histological analyses were performed to assess endothelial function. Diabetic rats showed significantly inhibited cardiac function and EDR, decreased expression of serum NO and phosphorylation at Ser(1177) on endothelial NOS (eNOS), and impaired endothelial integrity after 8 weeks. Chronic treatment for 8 weeks with either QL or Ben prevented the inhibition of cardiac function and EDR and the decrease in serum NO and eNOS phosphorylation caused by diabetes. Moreover, either QL or Ben suppressed inducible NOS (iNOS) protein levels as well as endothelial necrosis compared with the diabetic rats. Additionally, QL prevented the increase in angiotensin-converting enzyme 1 and angiotensin II receptor type 1 in diabetes. Thus, chronic administration of QL improved serum NO production, EDR, and endothelial integrity in diabetic rat aortas, possibly through balancing eNOS and iNOS activity and decreasing renin-angiotensin system expression.

[Qingli shengjing pills decrease apoptosis of germ cells and expressions of fas and fasL in male mice infected with Escherichia coli].

OBJECTIVE: To study the effects of Qingli Shengjing Pills (QSP) on the apoptosis of germ cells and expressions of Fas and FasL in male mice infected with Escherichia coli (E. coli), and to clarify the molecular mechanism of QSP in the treatment of male infertility induced by E. coli infection. METHODS: Fifty male mice were injected with E. coli via the bladder to make infection models, and at 15 dpi equally randomized into five groups: an untreated, a high-dose QSP (22.5 g/ml), a medium-dose QSP (13.5 g/ml), a low-dose QSP (4.50 g/ml) and a Furadantin treatment group, which were coded as MN, MTa, MTb, MTc and MTd, respectively. Another 10 mice were injected with saline and included in the control group coded as CT. After 10 days of oral medication, the apoptosis of germ cells in the testis of the mice was detected by flow cytometry, the expressions of Fas and FasL determined by immunohistochemistry and the histopathological changes observed simultaneously. RESULTS: After the treatment, the apoptosis of germ cells was observed in all the infected groups, and the apoptosis level in MN (57.44%) was significantly higher than that in CT (28.54%), MTb (28.59%) or MTa (30.11%) (P < 0.01) but had no significant difference from that in MTc (46.54%) or MTd (43.41%) (P > 0.05). The expressions of Fas and FasL proteins were significantly higher in MN than in CT, MTa, MTb, MTc and MTd (P < 0.01). Histopathological changes of the testis tissue were observed in MN, but not in other groups. CONCLUSION: E. coli infection could increase the apoptosis rate of germ cells and the expressions of Fas and FasL proteins. Qingli Shengjing Pills, capable of enhancing reproductivity by reducing the expressions of Fas and FasL and apoptosis of germ cells, can be used as one of the effective drugs for infertility induced by E. coli infection.

Dual effects of sodium aescinate on vascular tension in rat thoracic aorta.

OBJECTIVE: Sodium aescinate (SA) is used as a vasoactive drug in clinical treatment. This study was designed to investigate the effects of SA on rat isolated thoracic aorta and the possible mechanisms. METHODS: Isometric tension was recorded in response to drugs in organ bath. RESULTS: The effects of SA obeyed an all-or-nothing response. SA in relatively low dose (> or = 50 microg/ml) had an endothelium-independent contractile effect in rat aorta (P<0.01), which depended on extracellular Ca(2+) influx via L-type Ca(2+) channel (P<0.05). SA in relatively high dose (> or = 100 microg/ml) also induced vasoconstriction in Ca(2+)-free medium (P<0.01), which was independent of the activity of inositol-1,4,5-trisphosphate receptor (IP(3)R), ryanodine receptor (RYR), and protein kinase C (PKC). SA in relatively high dose (> or = 100 microg/ml) dilated both endothelium-intact and endothelium-denuded aortic rings precontracted by phenylephrine (PE) or KCl (each P<0.01). SA inhibited extracellular Ca(2+) influx induced by PE or KCl (each P<0.01) and had no activation effect on K(+) channels on vascular smooth muscle. The relaxant effect of SA partly depended on the activity of NO synthase but not on the activity of cyclooxygenase. CONCLUSIONS: Taken together, this study indicated that SA had dual effects on vascular tension in rat isolated thoracic aorta.

[Protection effect of Wenxin Keli on isoproterenol induced heart failure in rats].

OBJECTIVE: To study the treatment effect of Wenxin Keli on isoproterenol (ISO) induced heart failure in rats. METHOD: Sixty six-week old male Wistar rats were randomized into six groups. The rats in control group were only receive distilled water every day. The rats in ISO group also received two subcutaneous injections (85 mg x kg(-1)) of ISO, which were separated by a 24 hour interval and began to receive distilled water 2 weeks later every day. The rats in Wenxin Keli and control group were receive Wenxin Keli (9 mg x kg(-1)) every day. The rats in Wenxin Keli and ISO group received two subcutaneous injections (85 mg x kg(-1)) of ISO, which were separated by a 24 hour interval and began to receive Wenxin Keli (9 mg x kg(-1)) 2 weeks later every day. The rats in valsartan and control group were receive valsartan every day. The rats in valsartan and ISO group received two subcutaneous injections (85 mg x kg(-1)) of ISO, which were separated by a 24 hour interval and began to receive valsartan 30 mg x kg(-1) 2 weeks later every day. Echocardiogram measurement in rats were carried out after 4 weeks and 10 weeks feeding medince of hemodynamic measurement and aconitine induced arrhythmia in rats were carried out after 10 weeks. RESULT: Echocardiogram indicated that left ventricular internal diameter at diastolic phase (LVIDd), left ventricular internal diameter at systolic phase (LVIDs), LV percent fractional shortening (FS) and LV ejection fraction (EF) were decreased in the ISO group. Treatment with valsartan 4 weeks later, FS and EF were increased compared with the ISO group and 10 weeks later, LVIDd, LVIDs, FS, EF were increased. However, treatment with Wenxin Keli 10 weeks later, LVIDs, FS, EF were not changed obviously. Hemodynamic measurement showed that left ventricular end diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), and dp/dt(max) were improved after 10 weeks of treatment with valsartan. The LVEDP was decreased and dp/dt(max), was increased after 10 weeks of treatment with Wenxin Keli. Aconitine induced arrhythmia in rats in Wenxin Keli and control group were less serious than those in control group, aconitine induced arrhythmia in rats in Wenxin Keli and ISO group were less serious than those in ISO group. CONCLUSION: Wenxin Keli could greatly improve the ISO induced cardiac dysfunction and protect the aconitine-induced arrhythmia in rats.

Effects of Astragalus membranaceus and its main components on the acute phase endothelial dysfunction induced by homocysteine.

OBJECTIVE: This study was designed to investigate the effects of Astragalus membranaceus (AM) and its main components, astragalus saponin (ASP), astragalus polysaccharide (APS) and aminobutyric acid (GABA), on homocysteine (Hcy) induced acute impairment of vascular tone and to explore whether the antioxidant mechanism was involved in AM protective effect. METHODS: Inhibitory effects of Hcy and protective effects of AM and its main components on endothelium-dependent relaxation of aortic rings were determined by isometric tension recordings and nitric oxide signaling was assayed with 125I-cGMP RIA Kit. Furthermore, generation of reactive oxygen species (ROS) in endothelial cells was detected using 5-(6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H2DCF-DA). RESULTS: Hcy significantly inhibited endothelium-dependent relaxation to acetylcholine (ACh) in a dose-dependent manner, and decreased cGMP levels increased by ACh in aorta. Furthermore, superoxide dismutase (SOD), AM, and ASP markedly attenuated inhibition of vasorelaxation and downregulation of cGMP level by Hcy, and APS exerted a tendency to reverse both of the depressive responses, while GABA had no similar effects. Additionally, partially impaired relaxation by Hcy was completely blocked due to the presence of N(omega)-nitro-L-arginine-methyl ester (L-NAME), which could not be further altered by treatment with AM, ASP, APS or GABA. Finally, Hcy significantly increased intracellular ROS levels in endothelial cells as measured by CM-H2DCF-DA fluorescence. SOD, AM, ASP, and APS, but not GABA, inhibited Hcy-stimulated ROS generation. CONCLUSION: This study demonstrated that AM and ASP, potently protected endothelium-dependent relaxation against the acute injury from Hcy through nitric oxide regulatory pathways, in which antioxidation played a key role.

[Ixeris sonchifolia induced vasoconstriction effect and its mechanism in rat thoracic aorta].

OBJECTIVE: To investigate the vasoconstriction effect of Ixeris sonchifolia in rat thoracic aortic rings and the underlying mechanisms. METHOD: I. sonchifolia 10-160 g x L(-1) was cumulatively added into organ bath to observe the isometric tension of thoracic aortic rings with intact endothelium or denuded endothelium in basal tension, preconstricted by phenylephrine (PE) or potassium chloride (KCl), and thoracic aortic rings with intact endothelium preincubated frist with captopril, phosphoramidon and indomethacin, respectively, then preconstricted by PE and KCl. The response was recorded and expressed by "relative contraction". RESULT: Cumulative administration of I. sonchifolia 10-160 g x L(-1) did not affect the vasomotion of aortic rings with endothelium or without endothelium in basal tension. Exposure of intact endothelium rings preconstricted by PE or KCl to I. sonchifolia at concentration (20-160 g x L(-1) induced a significant constriction, which was inhibited by preincubation with captopril, but was not inhibited by preincubation with phosphoramidon or indomethacin. Exposure of endothelium-denuded rings preconstricted by PE or KCl to I. sonchifolia at concentration (10 to approximately 160 g x L(-1) did not effect the vasoconstriction. CONCLUSION: The results indicate that I. sonchifolia (20 to approximately 160 g x L(-1) can contract the rat thoracic aortic rings with endothelium. The effect of contraction may enhance angiotensin converting enzyme activity and promote endothelium to synthesize angiotensin II. It has no relationship to endothelin or thromboxane A2.

Protection effect of Wenxin Keli on isoproterenol induced heart failure in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study the treatment effect of Wenxin Keli on isoproterenol (ISO) induced heart failure in rats.</p><p><b>METHOD</b>Sixty six-week old male Wistar rats were randomized into six groups. The rats in control group were only receive distilled water every day. The rats in ISO group also received two subcutaneous injections (85 mg x kg(-1)) of ISO, which were separated by a 24 hour interval and began to receive distilled water 2 weeks later every day. The rats in Wenxin Keli and control group were receive Wenxin Keli (9 mg x kg(-1)) every day. The rats in Wenxin Keli and ISO group received two subcutaneous injections (85 mg x kg(-1)) of ISO, which were separated by a 24 hour interval and began to receive Wenxin Keli (9 mg x kg(-1)) 2 weeks later every day. The rats in valsartan and control group were receive valsartan every day. The rats in valsartan and ISO group received two subcutaneous injections (85 mg x kg(-1)) of ISO, which were separated by a 24 hour interval and began to receive valsartan 30 mg x kg(-1) 2 weeks later every day. Echocardiogram measurement in rats were carried out after 4 weeks and 10 weeks feeding medince of hemodynamic measurement and aconitine induced arrhythmia in rats were carried out after 10 weeks.</p><p><b>RESULT</b>Echocardiogram indicated that left ventricular internal diameter at diastolic phase (LVIDd), left ventricular internal diameter at systolic phase (LVIDs), LV percent fractional shortening (FS) and LV ejection fraction (EF) were decreased in the ISO group. Treatment with valsartan 4 weeks later, FS and EF were increased compared with the ISO group and 10 weeks later, LVIDd, LVIDs, FS, EF were increased. However, treatment with Wenxin Keli 10 weeks later, LVIDs, FS, EF were not changed obviously. Hemodynamic measurement showed that left ventricular end diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), and dp/dt(max) were improved after 10 weeks of treatment with valsartan. The LVEDP was decreased and dp/dt(max), was increased after 10 weeks of treatment with Wenxin Keli. Aconitine induced arrhythmia in rats in Wenxin Keli and control group were less serious than those in control group, aconitine induced arrhythmia in rats in Wenxin Keli and ISO group were less serious than those in ISO group.</p><p><b>CONCLUSION</b>Wenxin Keli could greatly improve the ISO induced cardiac dysfunction and protect the aconitine-induced arrhythmia in rats.</p>

Ixeris sonchifolia induced vasoconstriction effect and its mechanism in rat thoracic aorta / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the vasoconstriction effect of Ixeris sonchifolia in rat thoracic aortic rings and the underlying mechanisms.</p><p><b>METHOD</b>I. sonchifolia 10-160 g x L(-1) was cumulatively added into organ bath to observe the isometric tension of thoracic aortic rings with intact endothelium or denuded endothelium in basal tension, preconstricted by phenylephrine (PE) or potassium chloride (KCl), and thoracic aortic rings with intact endothelium preincubated frist with captopril, phosphoramidon and indomethacin, respectively, then preconstricted by PE and KCl. The response was recorded and expressed by "relative contraction".</p><p><b>RESULT</b>Cumulative administration of I. sonchifolia 10-160 g x L(-1) did not affect the vasomotion of aortic rings with endothelium or without endothelium in basal tension. Exposure of intact endothelium rings preconstricted by PE or KCl to I. sonchifolia at concentration (20-160 g x L(-1) induced a significant constriction, which was inhibited by preincubation with captopril, but was not inhibited by preincubation with phosphoramidon or indomethacin. Exposure of endothelium-denuded rings preconstricted by PE or KCl to I. sonchifolia at concentration (10 to approximately 160 g x L(-1) did not effect the vasoconstriction.</p><p><b>CONCLUSION</b>The results indicate that I. sonchifolia (20 to approximately 160 g x L(-1) can contract the rat thoracic aortic rings with endothelium. The effect of contraction may enhance angiotensin converting enzyme activity and promote endothelium to synthesize angiotensin II. It has no relationship to endothelin or thromboxane A2.</p>

Diphasic effects of Astragalus membranaceus BUNGE (Leguminosae) on vascular tone in rat thoracic aorta.

This study was designed to investigate the effects of the aqueous ethanol extract of Astragalus membranaceus BUNGE (Leguminosae) on rat thoracic aorta. Isometric tension was recorded in response to drugs in organ bath. In endothelium-intact aortic rings, A. membranaceus extract induced a significant dose-dependent relaxation of the rings precontracted by phenylephrine, which could be inhibited by preincubation with L-N(omega)-nitro-arginine methyl ester or methylthioninium chloride. In endothelium-denuded ones, the extract could dose-dependently relax the rings contracted by phenylephrine, not by KCl; and it could also attenuate contractile response to phenylephrine, not to caffeine or phorbol-12,13-diacetate in Ca(2+)-free medium; but it failed to affect the CaCl(2)-induced enhancement of contractile response to phenylephrine in Ca(2+)-free medium. These results indicate that nitric oxide signaling and Ca(2+)-handling pathway are involved in the A. membranaceus extract-induced vasodilatation.

Comparison of low and high doses of carvedilol on restoration of cardiac function and calcium-handling proteins in rat failing heart.

1. The beta-adrenoceptor antagonist carvedilol reverses cardiac dysfunction in the failing heart. A recent study showed that beta-adrenoceptor antagonists indirectly normalize Ca(2+)-regulatory proteins. The relationship between these two phenomena and the suitable dosage of carvedilol remains unclear. 2. We investigated the change in left ventricular (LV) remodelling and function in a rat model of heart failure due to myocardial infarction (MI) with or without carvedilol (30 or 2 mg/kg per day) treatment for 6 weeks. The expression of mRNA and proteins of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and phospholamban (PLB) in cardiomyocytes was also measured. 3. There was significant LV remodelling and cardiac contractile dysfunction in MI rats. The expression of SERCA mRNA and protein were downregulated (P < 0.01), but the expression of PLB mRNA and protein were upregulated (P < 0.01) in MI rats compared with sham-operated rats. After treatment with carvedilol, LV remodelling and cardiac contractile dysfunction were clearly improved. Low-dose carvedilol was better at improving some parameters of LV remodelling and function than the high dose. Carvedilol partially restored the low expression of SERCA (P < 0.05), but had no effect on PLB expression (P > 0.05). Moreover, low-dose carvedilol induced a more significant improvement in SERCA expression than did the high dose (P < 0.05). 4. The results of the present study suggest that carvedilol is effective in improving LV remodelling and cardiac contractile dysfunction after MI. This may be related to the normalization of SERCA expression.

[Relaxant effect of Astragalus membranaceus on smooth muscle cells of rat thoracic aorta].

OBJECTIVE: To investigate the effect of Astragalus membranaceus(AM) on vascular circles and the underlying mechanisms. METHODS: The study was performed with the model of isolate rat thoracic aorta rings in organ bath. When the endothelium of rat thoracic aorta was removed,the effect of accumulated AM on aorta rings in resting tension, or pre-constricted with KCl, or pre-constricted with phenylephrine (PE) was observed. And to explove the mechanism, the aorta rings were incubated with Ca(2+)-free medium alone, or Ca(2+)-free medium plus heparin, or propranolol alone before pre-contraction with PE. RESULTS: AM had no significant effects on aorta rings in resting tension or pre-constricted with KCl. When the concentration of AM was cumulated to 10(-1), 3 x 10(-1),10(0), 3 x 10(0) g/L, it caused concentration-dependent relaxation while aorta rings were pre-constricted with PE(3 x 10(-7)mol/L), compared with the control [(90.4 +/-4.2)% compared with (94.7 +/-2.4)%,(86.1 +/-5.0)% compared with (92.6 +/-3.2)%, (82.3 +/-5.9)% compared with (90.4 +/-3.6) %, (78.3 +/-6.0)% compared with (88.1 +/-4.0)%]. This effect was not inhibited by Ca(2+)-free medium or propranolol alone. However, the effect was attenuated by the co-incubation with heparin and Ca(2+)-free medium [without heparin:(76.2+/-4.3)% compared with (92.3 +/-5.9)%, with heparin: (95.3+/-0.5)% compared with (95.1+/-0.6)%]. CONCLUSION: The results indicate that AM can relax the rat thoracic aorta rings without endothelium. The mechanism may include the inhibition of intracellular calcium ions release by the 1,4,5-triphosphate inositol-receptor-dependent pathway in vascular smooth muscle cells.

Relaxant effect of Astragalus membranaceus on smooth muscle cells of rat thoracic aorta / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of Astragalus membranaceus(AM) on vascular circles and the underlying mechanisms.</p><p><b>METHODS</b>The study was performed with the model of isolate rat thoracic aorta rings in organ bath. When the endothelium of rat thoracic aorta was removed,the effect of accumulated AM on aorta rings in resting tension, or pre-constricted with KCl, or pre-constricted with phenylephrine (PE) was observed. And to explove the mechanism, the aorta rings were incubated with Ca(2+)-free medium alone, or Ca(2+)-free medium plus heparin, or propranolol alone before pre-contraction with PE.</p><p><b>RESULTS</b>AM had no significant effects on aorta rings in resting tension or pre-constricted with KCl. When the concentration of AM was cumulated to 10(-1), 3 x 10(-1),10(0), 3 x 10(0) g/L, it caused concentration-dependent relaxation while aorta rings were pre-constricted with PE(3 x 10(-7)mol/L), compared with the control [(90.4 +/-4.2)% compared with (94.7 +/-2.4)%,(86.1 +/-5.0)% compared with (92.6 +/-3.2)%, (82.3 +/-5.9)% compared with (90.4 +/-3.6) %, (78.3 +/-6.0)% compared with (88.1 +/-4.0)%]. This effect was not inhibited by Ca(2+)-free medium or propranolol alone. However, the effect was attenuated by the co-incubation with heparin and Ca(2+)-free medium [without heparin:(76.2+/-4.3)% compared with (92.3 +/-5.9)%, with heparin: (95.3+/-0.5)% compared with (95.1+/-0.6)%].</p><p><b>CONCLUSION</b>The results indicate that AM can relax the rat thoracic aorta rings without endothelium. The mechanism may include the inhibition of intracellular calcium ions release by the 1,4,5-triphosphate inositol-receptor-dependent pathway in vascular smooth muscle cells.</p>

[Electrophysiologic study of the biphasic effects of cyclovirobuxine D on arrhythmias].

OBJECTIVE: To explore the possible mechanism of cyclovirobuxine D (CVB-D) in countering and inducing arrhythmia, by way of studying its electro-physiological effect on ventricular papillary muscles of rats in vitro. METHODS: The transmembrane potential of rat's isolated right ventricular papillary muscles were recorded using conventional glass micro-electrode technique. RESULTS: (1) CVB-D in concentration of 13.3-63.3 micromol/L, showed prolonging effect on the action potential repolarization time, mainly the action potential duration 50 (APD50), APD70 and APD90, in dose-dependent manner, in concentration of 33.3-63.3 micromol/L, it could inhibit the resting potential, action potential amplitude (APA) and maximum depolarization velocity (Vmax) in dose-dependent manner. (2) CVB-D also showed time-dependent effect, the effect initiated 10 min after 20 micromol/L was perfused in ventricular muscle, the APD50, APD70 and APD90 were potentiated gradually along with prolongation of action time and reached the peak at 30-40 min, without any potentiation thereafter. (3) CVB-D could markedly prolong the effective refractory period (ERP) of action potential, increase the ratio of ERP/APD. (4) CVB-D in concentration of 33.3 micromol/L could induce frequent, multifocal spontaneous arrhythmia in some cells when the action time was longer than 45 min. CONCLUSION: CVB-D has the action of anti-ventricular arrhythmia, the mechanism is correlated with the prolongation of APD and ERP of ventricular muscle as well as the increase of ERP/APD ratio, while it also has the effect of inducing arrhythmia, the mechanism might be concerned with excessive prolongation of APD and the inhibition on RP, APA and Vmax.

Electrophysiologic study of the biphasic effects of cyclovirobuxine D on arrhythmias / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the possible mechanism of cyclovirobuxine D (CVB-D) in countering and inducing arrhythmia, by way of studying its electro-physiological effect on ventricular papillary muscles of rats in vitro.</p><p><b>METHODS</b>The transmembrane potential of rat's isolated right ventricular papillary muscles were recorded using conventional glass micro-electrode technique.</p><p><b>RESULTS</b>(1) CVB-D in concentration of 13.3-63.3 micromol/L, showed prolonging effect on the action potential repolarization time, mainly the action potential duration 50 (APD50), APD70 and APD90, in dose-dependent manner, in concentration of 33.3-63.3 micromol/L, it could inhibit the resting potential, action potential amplitude (APA) and maximum depolarization velocity (Vmax) in dose-dependent manner. (2) CVB-D also showed time-dependent effect, the effect initiated 10 min after 20 micromol/L was perfused in ventricular muscle, the APD50, APD70 and APD90 were potentiated gradually along with prolongation of action time and reached the peak at 30-40 min, without any potentiation thereafter. (3) CVB-D could markedly prolong the effective refractory period (ERP) of action potential, increase the ratio of ERP/APD. (4) CVB-D in concentration of 33.3 micromol/L could induce frequent, multifocal spontaneous arrhythmia in some cells when the action time was longer than 45 min.</p><p><b>CONCLUSION</b>CVB-D has the action of anti-ventricular arrhythmia, the mechanism is correlated with the prolongation of APD and ERP of ventricular muscle as well as the increase of ERP/APD ratio, while it also has the effect of inducing arrhythmia, the mechanism might be concerned with excessive prolongation of APD and the inhibition on RP, APA and Vmax.</p>

[Effect of Astragalus membranaceus on baroreflex sensitivity in spontaneously hypertensive rats].

OBJECTIVE: To observe the chronicity decompression effect of Astragalus Membranaceus(AM) and evaluate the effect on baroreflex sensitivity (BRS). METHOD: Nineteen spontaneously hypertensive rats(SHR) were randomly divided into four groups. The AM groups were intraperitoneally administered with AM parenteral solution 0.9 mL, 1.2 mL and 1.8 mL respectively and the control group was not given AM for eight weeks. Then the change of blood pressure was observed successivly. After eight weeks, BRS were also determined. At last, the difference of blood pressure and BRS among the groups were compared. RESULT: Blood pressure in the control group became higher and higher frome the third week to the eighth week, but the other SHR admistered with AM showed no changein blood pressure level. We also found that the BRS in AM group was higher than that in the control group(P < 0.01). CONCLUSION: AM can promote the BRS in SHR.