Semen Cuscutae-Fructus Lycii improves spermatogenic dysfunction by repairing the blood-testis barrier in rats according to in silico and in vitro methods.

ETHNOPHARMACOLOGICAL RELEVANCE: Semen Cuscutae and Fructus Lycii (SC-FL) is a commonly used herbal pair for male infertility treatment. Studies have found that the mechanism of SC-FL treatment may be related to repairing the blood-testis barrier (BTB). The application of network pharmacology can be used to explore the correlation between medicines and diseases and predict the potential pharmacological mechanisms of SC-FL. AIM OF THE STUDY: This study aimed to explore the specific effects and mechanisms of SC-FL in repairing the BTB and initially revealed the mechanism of Chinese medicine treating male infertility through network pharmacology and animal experiments. MATERIALS AND METHODS: We searched databases using the network pharmacology method and performed mass spectrometry analysis. We analyzed and predicted the active ingredients, targets and key pathways of SC-FL in male infertility treatment. Then, we designed animal experiments to verify the results. Thirty-six Sprague-Dawley rats were randomly divided into the normal control group (NC group), spermatogenic dysfunction group (SD group) and SC-FL treatment group (SCFL group). Glucosides of Tripterygium wilfordii Hook. F (GTW) (40 mg/kg/d) was administered for 4 weeks to generate a spermatogenic dysfunction model. The rats in the SCFL group were given the SC-FL suspension (6 g/kg/d) daily. After 4 weeks of treatment, we detected the sperm quality of each group of rats and observed the cell morphology. Western blotting and qRT-PCR were used to detect the expression of BTB-related proteins in testicular tissues. RESULTS: 213 chemical ingredients of SC and FL were retrieved from the TCMSP database, and 54 effective chemical ingredients were obtained. Mass spectrometry analysis showed the above results were credible. Then, we identified 44 potential targets for the treatment of male infertility, and we plotted a network diagram of the interaction network between the core targets and a diagram of herbal medicine-active ingredient-target-disease interactions. The target genes were enriched according to biological functions, and 22 biological processes, 49 cellular components, 1487 molecular functions, and 122 signaling pathways were obtained. The results of the animal experiments showed that the sperm concentration and motility of the SCFL group were significantly improved compared with those of the SD group. Compared with those in the SD group, the structure and morphology of the Sertoli cells and seminiferous tubules of rats in the SCFL group improved, and the number of spermatogenic cells increased significantly. Western blotting and qRT-PCR results showed that compared with that in the SD group, the expression of p38 MAPK decreased significantly, and the expression of c-Jun, Occludin, ZO-1 and connexin 43 increased significantly in the SCFL group. CONCLUSION: We predicted that the active ingredients of SC-FL can treat male infertility by interacting with the core targets JUN, IL6, MAPK1, TP53, MYC, CCND1, AR, EGF, FOS, and MAPK8, and the possible mechanism is related to the MAPK signaling pathway. SC-FL can regulate the MAPK pathway and affect the expression of Occludin, ZO-1 and connexin 43 to repair damaged BTB and improve spermatogenic dysfunction induced by GTW, which may be one of the possible mechanisms.

Effect of Bushen Huoxue recipe on women with thin endometrial ovulation disorder and a rat model of thin endometrium resulted from kidney deficiency-related blood stasis.

To examine the therapeutic effect of Bushen Huoxue recipe (BHR) on women with thin endometrial ovulation disorder and on a rat model of kidney deficiency-related blood stasis. A total of 60 women with thin endometrial ovulation disorder was enrolled. The primary outcome of the study was the pregnancy rate three menstrual cycles after treatment. The study also examined the changes in the type and thickness of uterine artery, uterine artery pulsatility index (PI) and endometrial resistance index (RI). To establish kidney deficiency-related blood stasis in Sprague Dawley (SD) rats, an intragastric administration of hydroxyurea and a tail vein injection of Dextran were given, following with a flashing of the uterine cavity with 95% anhydrous ethanol. A combined regimen of BHR and estradiol valerate significantly increased the rate of pregnancy in women with thin endometrial ovulation disorder. The treatment was accompanied by a significant increase in endometrial thickness and decreases in uterine artery PI and endometrial RI. In rats, kidney deficiency-related blood stasis caused severe loss in endometrial architecture, thickness, and numbers of gland and blood vessel compared to the healthy SD rats. Treatment with BHR could ameliorate the endometrial damages associated with kidney deficiency-related blood stasis.

A combination of Semen Cuscutae and Fructus Lycii improves testicular cell proliferation and inhibits their apoptosis in rats with spermatogenic dysfunction by regulating the SCF/c-kit--PI3K--Bcl-2 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Semen Cuscutae is the seed of Cuscuta japonica Choisy, and Fructus Lycii is the mature fruit of Lycium barbarum L. (Solanaceae). Semen Cuscutae and Fructus Lycii (SC-FL) are well-known Chinese medicine which have been used to tonify the kidney and replenish the essence for thousands of years. Chinese physicians prefer to prescribe them for treating male infertility. Recent studies have found that SC-FL repair spermatogenic dysfunction, however, the therapeutic mechanism has yet to be clearly elucidated. AIM OF THE STUDY: This study aimed at evaluating the therapeutic effect of SC-FL in glucosides of Tripterygium wilfordii Hook. f (GTW)-induced dyszoospermia rats and elucidating the underlying molecular mechanism. MATERIALS AND METHODS: Seventy-eight Sprague-Dauley (SD) rats were randomly divided into five groups: normal control (treated with saline), GTW (treated with saline), GTW + levocarnitine (treated with levocarnitine), GTW + SCFL (treated with SC-FL), and LY (LY294002, the PI3K inhibitor) +SCFL (treated with SC-FL). GTW (40 mg/kg/d) was intragastrically administered for 4 weeks to establish dyszoospermia model. From the start of the study, LY was additionally injected into the tail vein of rats of the LY + SCFL group once a week. After 8 weeks, semen quality and organ coefficient were determined and sex hormone, inhibin B, and epididymal carnitine levels were measured. Testicular tissue and its ultrastructure were observed using H&E (hematoxylin-eosin) staining and electron microscopy. Immunohistochemistry, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to determine the protein and mRNA expression of SCF, c-kit, PI3K, p-Akt, Bad, Bcl-2, and Bax in rat testis. RESULTS: Compared with the GTW group, semen quality, the organ coefficient, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and epididymal carnitine levels were significantly improved in the GTW + SCFL group (P < 0.05 or P < 0.01). Histomorphology and testicular ultrastructural evaluation showed that in the GTW + SCFL group, the structure and arrangement of seminiferous tubules were better, the amount of spermatogenic cells increased significantly, the morphology of spermatogenic cells improved, and the mitochondria increased, compared to those in the GTW group. Immunohistochemistry, western blotting, and qRT-PCR results showed that compared with the GTW group, the expression of SCF, c-kit, PI3K, p-Akt, and Bcl-2 in the GTW + SCFL group was increased, while that of Bax and Bad was decreased. The expression of p-Akt and Bcl-2 decreased, while that of Bad and Bax increased in the LY + SCFL group compared with the SCFL group. CONCLUSION: SC-FL can effectively inhibit spermatogenic cell apoptosis and promote their proliferation, and the mechanism may be related to the regulation of the SCF/c-kit--PI3K--Bcl-2 pathway.

Effects of Zuogui Wan on testis structure and expression of c-Kit and Oct4 in rats with impaired spermatogenesis.

CONTEXT: Zuogui Wan is a classic traditional Chinese prescription. Preliminary studies have confirmed that it could improve sperm quality significantly. OBJECTIVE: To investigate the effect of Zuogui Wan on testis structure and c-kitproto-oncogeneprotein (c-Kit) and octamer-binding transcription factor-4 (Oct4) expression in a rat model of impaired spermatogenesis. MATERIAL AND METHODS: Thirty-six Sprague-Dawley (SD) rats were divided into Blank control, Tripterygium glycosides (GTW) and Zuogui Wan groups (n = 12). GTW was used to generate models of impaired spermatogenesis. Then Zuogui Wan group was administered 6 g/kg/d of Zuogui Wan granules for 4 weeks. Changes in the pathological structure and ultrastructure were observed with optical microscope and transmission electron microscope. Expression of c-Kit and Oct4 were quantified by RT qPCR and Western blots. RESULTS: Both the pathological damage and the damages in the ultrastructure of spermatogenic epithelium had improved in Zuogui Wan group. Compared with the GTW model group (0.47 ± 0.19; 0.38 ± 0.14), c-Kit and Oct4 protein expression increased in the Zuogui Wan group (0.75 ± 0.27; 0.65 ± 0.23). C-Kit and Oct4 mRNA expression increased in Zuogui Wan group (1.06 ± 0.16; 1.85 ± 1.04) compared to the GTW model group (0.66 ± 0.23; 0.46 ± 0.29). CONCLUSIONS: Zuogui Wan is capable of restoring the damage to the testis structure and ultrastructure and regulates the expression of c-Kit and Oct4 at protein and mRNA levels, inhibiting apoptosis and promoting proliferation of spermatogenic cells.

Paeoniflorin ameliorates glycemic variability-induced oxidative stress and platelet activation in HUVECs and DM rats.

Glycemic variability (GV) plays an important role in the pathogenesis of vascular complications associated with diabetes mellitus (DM). Paeoniflorin is an effective Chinese traditional medicine with anti-inflammatory and immune-regulatory effects. Previous studies implicated the beneficial effects of paeoniflorin in treatment for diabetic complications, such as type 2 diabetic nephropathy and diabetes with myocardial ischemic injury. Current evidence suggests that oxidative stress and platelet activation, as well as their interaction, are potentially associated with GV and involved in the pathogenesis of diabetes-associated vascular complications. This study aimed to explore the effects of paeoniflorin on oxidative stress and platelet activation, using human umbilical vein endothelial cells (HUVECs) cultured with different glucose concentrations, and streptozotocin-induced diabetic rats fed different glycemic index diets. Paeoniflorin treatment effectively improved the morphology and cell viability of HUVECs under glucose fluctuation. Moreover, the platelet aggregation rate, CD62p expression, and reactive oxygen species (ROS) concentration decreased, while glutathione peroxidase (GSH-px) levels increased in paeoniflorin-treated groups. In conclusion, our study found that paeoniflorin ameliorates oxidative stress and platelet activation induced by glycemic variability both in vivo and in vitro, suggesting a novel potential strategy for treatment of diabetic complications.

Effectiveness comparisons of acupuncture for chronic prostatitis/chronic pelvic pain syndrome: A Bayesian network meta-analysis protocol.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urinary system disease in the male population. Recent studies have shown that acupuncture can alleviate the pain caused by CP/CPPS to a certain extent and improve the quality of life of patients. This study used a network meta-analysis (NMA) to compare the effectiveness and safety of different forms of acupuncture on CP/CPPS. METHODS AND ANALYSIS: We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online and China Journal Full-text Database, China Biomedical Literature CD-ROM Database, and related randomized controlled trials (RCTs) included in the China Resources Database. The time is limited from the construction of the library to December 2018. The quality of the included RCTs will be evaluated with the risk of bias tool and evidence will be evaluated by grading of recommendations assessment, development, and evaluation. STATA 13.0 and WinBUGS 1.4.3 through the GeMTC package will be used to perform a NMA to synthesize direct and indirect evidence. RESULTS: The results of this NMA will be submitted to a peer-reviewed journal for publication. TRIAL REGISTRATION NUMBER: PROSPERO CRD42018111408.

The Influence of Hyperlipidemia on Endothelial Function of FPN1 Tek-Cre Mice and the Intervention Effect of Tetramethylpyrazine.

BACKGROUND/AIMS: Systemic iron homeostasis is strictly governed in mammals; however, disordered iron metabolism (such as excess iron burden) is recognized as a risk factor for various types of diseases including AS (Atherosclerosis). The hepcidin-ferroportin axis plays the key role in regulation of iron homeostasis and modulation of this signaling could be a potential therapeutic strategy in the treatment of these diseases. TMP (Tetramethylpyrazine) has been reported to have therapeutical effect on AS. Here, we aimed to investigate the effect of iron overload under hyperlipidemia condition on the endothelial injury, inflammation and oxidative stress by employing FPN1 Tek-cre mouse model with or without TMP intervention. METHODS: Subjects for this study were 80 FPN1 Tek-cre mice and 40 C57BL/6 mice and we randomly divided them into six groups: Group N: C57BL/6 mice with normal diet, Group M: C57BL/6 mice with high-fat diet, Group FN: FPN1 Tek-cre mice with normal diet, Group FNT: FPN1 Tek-cre mice with normal diet and TMP injection, Group FM: FPN1 Tek-cre mice with high-fat diet, Group FMT: FPN1 Tek-cre mice with high-fat diet and TMP injection. After seven days of treatment, blood samples were obtained to detect the levels of blood lipids, Hepcidin, NO, ET-1, ROS, MDA, SOD, IL-1, IL-6 and TNF-α respectively. The liver and aorta were used for testing the lipid deposition by using hematoxylin and eosin(HE). RESULTS: Hyperlipidemia could cause iron overload in the aorta and increased serum hepcidin level, particularly in FPN1 Tek-cre mice, and can be reversed by TMP intervention. Knockout of Fpn1 induced increase of serum hepcidin, exacerbated endothelial dysfunction, oxidative stress and inflammatory response, particularly under hyperlipidemia condition. TMP intervention attenuated these processes. CONCLUSIONS: Our study signifies the potential application of certain natural compounds to ameliorating iron disorders induced by hyperlipidemia and protecting on endothelial function through modulation of hepcidin-ferroportin signaling.

Wenshen Yangxue decoction improves endometrial receptivity recovery and promotes endometrial angiogenesis in a rat model.

CONTEXT: Wenshen Yangxue decoction (WSYXD) is a famous traditional Chinese medicine (TCM) formula and has been used in infertility treatment, but the exact mechanism is still unknown. OBJECTIVES: To determine if WSYXD improves endometrial receptivity recovery and promotes endometrial angiogenesis in a rat model. MATERIALS AND METHODS: A total of 100 proestrus female SPF Wistar rats were randomly assigned into five groups: control (saline), model (saline and hydroxyurea solution), high (5.2/100 g), middle (2.6/100 g) and low (1.3/100 g) WSYXD dose groups for 10 d. The microvessel densities, endometrial microstructure, as well as blastocysts number, were observed, followed by detection of angiogenesis-related gene/protein expression by immunohistochemistry, western blot and quantitative real-time polymerase chain reaction (RT-PCR), respectively. RESULTS: Compared with the model group, the blastocyst number in WSYXD middle and high groups were significantly increased (4.50 ± 3.11 vs. 13.00 ± 2.12, 14.00 ± 1.83, p < 0.01). Lower MVD can be found in the model group (4.7) when compared with the normal control (13.7), middle (8.4) and high (9.7) dose groups. Additionally, significant differences were observed in VEGF, HIF-1α, p-AKT, p-PI3K, Ang1 and Ang2 (all p < 0.01) among different groups. DISCUSSION AND CONCLUSIONS: In conclusion, WSYXD could help endometrial receptivity recovery and promote endometrial angiogenesis through PI3K, HIF-1α signalling and VEGF expression regulation. This study provides molecular evidence for application of WSYXD in the clinic and promotes new drug development from TCM.

[Correlation Research on Blood Glucose Fluctuation in Type 2 Diabetes Mellitus Patients and Vas- cular Endothelial Injury/Platelet Activation/PKCß1 Expression].

Objective To observe the correlation between blood glucose fluctuation in type 2 dia- betes mellitus ( T2DM) patients and vascular endothelial injury/platelet activation/protein kinase Cß1 (PKCpß1). Methods Capillary blood was collected from finger tips of 38 T2DM patients at 7 time points, i.e., before 3 meals, 2 h after 3 meals, 21:00 pm before sleep. The mean amplitude of plasma glucose excursions (MAGE) was calculated. The peripheral blood platelet aggregation rate (PAG) induced by a- denosine diphosphate (ADP) and platelet membrane protein level of CD62p were determined by platelet fluorescent aggregometer and flow cytometry respectively. HbAlc was measured by ion-exchange high- performance liquid chromatography. Serum levels of E-selectin, von Willebrand factor ( vWF), and PKCß1 were detected by ELISA. Meanwhile, liver and renal functions, blood lipids were also measured. Their blood pressure was measured and body mass index (BMI) calculated. By taking HbA1c as a moni- tored index for assessing long-term glucose control, MAGE as an indicator for assessing glucose fluctua- tion, the correlations between serum markers for vascular endothelial injury (levels of E-selectin and vWF)/platelet activation indices (PAG and CD62p expression) and PKCß1 level/MAGE respectively were analyzed using Pearson correlation analysis and multivariant Logistic regression. The correlations be- tween PKCß1 level and MAGE/HbA1 c were also analyzed. Results In simple correlation analysis, there were no significant correlations between age/BMI/course of disease/medical history/serum levels of E-se- lectin/vWF/PKCß1/PAG/CD62p expression and MAGE (P >0. 05). There were significant correlations be- tween vascular endothelial injury markers ( E-selectin and vWF)/platelet activation indicators ( PAG, CD62p expression) and MAGE (r =0. 468, 0. 609, 0. 451 , 0. 674; P <0. 01). There were significant corre- lations between PKCß1 and glucose assessment indicators (MAGE and HbA1c)/vascular endothelial inju- ry markers ( E-selectin and vWF) , platelet activation indicators ( PAG and CD62p expression) (r = 0. 643, 0. 705, 0. 394, 0. 665, 0. 441 , 0. 577; P <0. 01). Conclusion PKCß1 , the key regulatory gene of coronary artery disease with blood stasis syndrome, was closely related with the degree of vascular en- dothelial injury and aggregation level of platelet activation in T2DM patients with blood glucose fluctuation.

Effects of Panax quinquefolium saponin on phosphatidylinositol 3-kinase/serine threonine kinase pathway of neonatal rat myocardial cells subjected to hypoxia.

OBJECTIVE: To explore the effects of Panax Quinquefolium Saponin (PQS) on phosphatidylinositol 3-kinase/serine threonine kinase (PI3K/Akt) pathway of neonatal rat myocardial cells subjected to hypoxia. METHODS: Neonatal rat myocardial cells were cultured in vitro. After the myocardial cell injury was induced by hypoxia, the cells were randomized into 5 groups: the normal group, the model group, the positive control group (Ciclosporin A, 2 µ mol/L), the low-dose PQS group (PQSL, 25mg/L), and the high-dose PQS group (PQSH, 50 mg/L). Morphology and behavior of myocardial cells were observed under an inverted microscope. Apoptosis rate and lactate dehydrogenase (LDH) leakage rate of myocardial cells were determined by colorimetry. Mitochondrial transmembrane potential was assessed using a fluorexon laser. Phospho-glycogen synthase kinase (GSK)-3ß and phospho-Akt as well as cytochrome C were determined by Western blot RESULTS: LDH leakage in the Ciclosporin A group, PQSH group and PQSL group reduced progressively compared with the model group (P<0.05). Akt and GSK-3ß was strongly phosphorylated after treatment with Ciclosporin A and PQS compared with the model group (P<0.05, P<0.01). Compared with the model group (16.41±1.74; 35.28±6.30), both the integrated optical density of mitochondrial permeability transition pore (MPTP) and the mitochondrial transmembrane potential significantly increased in the PQSH group (42.74±2.12; 71.36±6.54) and the PQSL group (39.58±1.49; 66.99±5.45; P<0.05, P<0.01). However, the protein of cytochrome C outside the mitochondrion decreased in the PQSH group (273.66±14.61) and the PQSL group (259.62±17.31) compared with the model group (502.41±17.76; P<0.05). CONCLUSION: Through activation of the PI3K/Akt pathway and inhibition of the MPTP, PQS might protect the heart against ischemia injury and apoptosis of myocardial cells.

[The estrogen-like protective effect of ginsenoside Rb3 on oxidative stress and dysfunction of endothelial cells induced by oxidized low-density lipoprotein].

Ginsenoside Rb3 (GRb3) is one of the main components in plasma of Panax quinquefolius Saponin of stem and leaf (PQS), which can be into human plasma. Previous studies have found PQS has estrogen-like vascular protective effects. In the present study, we investigated the estrogen-like protective effect of GRb3 on oxidative stress and dysfunction of endothelial cells induced by oxidized low-density lipoprotein. The activities of SOD, NOS and the contents of MDA in the cell lysate were examined by enzyme method or spectrophotometry. The NO and ET-1 concentrations in the cell culture supernatant were measured by ELISA method. The iNOS and eNOS mRNA expression were measured by real time RT-PCR, while the phosphorylation levels of Akt was measured by Western blotting. The results showed that GRb3 could enhance the activity of SOD, reduce the content of MDA, increase the level of NOS, NO, ET-1 and iNOS mRNA expression while decrease the eNOS mRNA expression and the phosphorylation level of Akt. These effects were blocked by estrogen receptor antagonist ICI182780. GRb3 can play a role in protecting vascular endothelial cells by estrogen receptors, the protective mechanism is similar to 17-ß estrodiol.

Panax Quinquefolius Saponin of Stem and Leaf Attenuates Intermittent High Glucose-Induced Oxidative Stress Injury in Cultured Human Umbilical Vein Endothelial Cells via PI3K/Akt/GSK-3 ß Pathway.

Panax quinquefolius saponin of stem and leaf (PQS), the effective parts of American ginseng, is widely used in China as a folk medicine for diabetes and cardiovascular diseases treatment. In our previous studies, we have demonstrated that PQS could improve the endothelial function of type II diabetes mellitus (T2DM) rats with high glucose fluctuation. In the present study, we investigated the protective effects of PQS against intermittent high glucose-induced oxidative damage on human umbilical vein endothelial cells (HUVECs) and the role of phosphatidylinositol 3-kinase kinase (PI3K)/Akt/GSK-3 ß pathway involved. Our results suggested that exposure of HUVECs to a high glucose concentration for 8 days showed a great decrease in cell viability accompanied by marked MDA content increase and SOD activity decrease. Moreover, high glucose significantly reduced the phosphorylation of Akt and GSK-3 ß . More importantly, these effects were even more evident in intermittent high glucose condition. PQS treatment significantly attenuated intermittent high glucose-induced oxidative damage on HUVECs and meanwhile increased cell viability and phosphorylation of Akt and GSK-3 ß of HUVECs. Interestingly, all these reverse effects of PQS on intermittent high glucose-cultured HUVECs were inhibited by PI3K inhibitor LY294002. These findings suggest that PQS attenuates intermittent-high-glucose-induced oxidative stress injury in HUVECs by PI3K/Akt/GSK-3 ß pathway.

The Expression of CD14(+)CD16(+) Monocyte Subpopulation in Coronary Heart Disease Patients with Blood Stasis Syndrome.

Blood stasis syndrome (BSS), a comprehensive pathological state, is one of the traditional Chinese medicine syndromes of coronary heart disease (CHD). In our previous study, we investigated that Fc γ RIIIA (also called CD14(+)CD16(+) monocyte subpopulation) is one of the differentially expressed genes related to CHD patients and its possible role in the atherosclerotic formation and plaque rupture. However, whether or not the deregulation of CD14(+)CD16(+) monocyte subpopulation expression is implicated in the pathogenesis of CHD patients with BSS has not yet been elucidated. In this study, we found that there was no significant difference between CHD patients with BSS and non-BSS in CD14(+)CD16(+) monocyte subpopulation at gene level. Moreover, the protein level of CD14(+)CD16(+) monocyte subpopulation in CHD patients with BSS was increased significantly when compared to the CHD patients with non-BSS. Additionally, the level of inflammatory cytokines downstream of CD14(+)CD16(+) monocyte subpopulation such as TNF- α and IL-1 in sera was much higher in CHD patients with BSS than that in CHD patients with non-BSS. Taken together, these results indicated that CD14(+)CD16(+) monocyte subpopulation was implicated in the pathogenesis of CHD patients with BSS, which may be one of the bases of the essence of BSS investigation.

Influence of high blood glucose fluctuation on endothelial function of type 2 diabetes mellitus rats and effects of Panax Quinquefolius Saponin of stem and leaf.

OBJECTIVE: To observe the influence of high blood glucose fluctuation on the endothelial function of type 2 diabetes mellitus (T2DM) rats and the effects of Panax Quinquefolius Saponin (PQS) of stem and leaf. METHODS: The T2DM model was induced by intraperitoneal injection of a small dose of streptozotocin (STZ, 35 mg/kg) plus high fat and high caloric laboratory chow. Then, diabetic rats were divided into steady high blood glucose (SHG) group and fluctuant high blood glucose (FHG) group according to fasting blood glucose coefficient of variation (FBG-CV), and then, the FHG group rats were divided into 4 groups according to the level of FBG-CV and fasting blood glucose: PQS 30 mg/(kg·d) group, PQS 60 mg/(kg·d) group, metformin hydrochloride control (MHC) group, and FHG control group, 10 in each group. Meanwhile, 10 rats without any treatment were used as normal control (NOR) group. Eight weeks later, the aortic arteries histology, plasma hepatocyte growth factor (HGF), and serum nitric oxide (NO), endothelin-1 (ET-1), tumor necrosis factor α (TNF-α), and soluble intercellular adhesion molecule 1 (sICAM-1) were measured. RESULTS: In comparison with the NOR group, the level of plasma HGF and serum NO, ET-1 and TNF-α, and sICAM-1 in SHG and FHG control groups were all significantly increased (P<0.01); in comparison with the SHG group, plasma HGF and serum NO, ET-1, TNF-α, and sICAM-1 in FHG group were all significantly increased further (P<0.01 or P<0.05); meanwhile, in comparison with the FHG control group, the level of plasma HGF and serum NO, ET-1, TNF-α, and sICAM-1 in PQS and MHC groups were all decreased significantly (P<0.01). However, comparison of the aortic arteries histology among groups showed no significant differences either before or after treatment. CONCLUSION: Blood glucose fluctuation could facilitate the development of vascular endothelial dysfunction in T2DM rats, while PQS could improve the endothelial function of T2DM rats with high blood glucose fluctuation, which may be related to its effects of relieving vessel stress, decreasing vasoconstrictor ET-1 production, preventing compensated increase of NO, and reducing inflammatory reaction.

Correlation between Fc γ R III a and aortic atherosclerotic plaque destabilization in ApoE knockout mice and intervention effects of effective components of chuanxiong rhizome and red peony root.

OBJECTIVE: To explore the correlation between Fc γ RIII A (CD16A) and aortic atherosclerotic plaque destabilization in apoE knockout (apoE KO) mice and the intervention effects of effective components of chuanxiong rhizome and red peony root. METHODS: Eight 8-week-old male C57BL/6J mice were selected as the control group. Forty 8-week-old male apoE KO mice were randomly divided into the model group, apoE KO + intraperitoneal injection immunoglobulin group (IVIG), apoE KO + simvastatin group (Sm), apoE KO + high dosage of xiongshao capsule (XSC) group (XSCH), and apoE KO + low dosage of XSC group (XSCL), 8 mice in each group. Mice in the control group were put on a normal diet, and others were fed with a high-fat diet. After 10-week different interventions, monocyte CD16 expression was detected by flow cytometry, aortic matrix metalloproteinase-9 (MMP-9) mRNA expression was detected using reverse transcription polymerase chain reaction, and serum tumor necrosis factor (TNF)-α level was detected using enzyme-linked immunosorbent assay. RESULTS: Compared with the control group, monocyte CD16 expression, aortic MMP-9 mRNA expression, and serum TNF-α level in the model group increased obviously (P<0.01). Injections of apoE KO mice with intraperitoneal immunoglobulin during a 5-day period significantly reduced the monocyte CD16 expression, aortic MMP-9 mRNA expression, and serum TNF-α level (P<0.01 or 0.05) over a 10-week period of high-fat diet. Indices above in the Sm group, XSCH group, and XSCL group decreased in a different degree. Of them, the aortic MMP-9 mRNA expression in XSCH group was lower than that in Sm group (P<0.05) and the monocyte CD16 expression and serum TNF-α level showed no significant difference between XSCH group and Sm group (P>0.05). Correlation analyses suggested positive correlation between monocyte CD16 expression and aortic MMP-9 mRNA expression or serum TNF-α level in IVIG group, XSCH group, and XSCL group. CONCLUSIONS: FcγR III A mediates systemic inflammation in the progression of coronary heart disease with blood stasis syndrome. XSC could stabilize atherosclerotic plaque by suppressing inflammation and its target was relative with FcγRIII A.