2-Deoxy-D-glucose ameliorates inflammation and fibrosis in a silicosis mouse model by inhibiting hypoxia-inducible factor-1α in alveolar macrophages.

Inhaling silica causes the occupational illness silicosis, which mostly results in the gradual fibrosis of lung tissue. Previous research has demonstrated that hypoxia-inducible factor-1α (HIF-1α) and glycolysis-related genes are up-regulated in silicosis. The role of 2-deoxy-D-glucose (2-DG) as an inhibitor of glycolysis in silicosis mouse models and its molecular mechanisms remain unclear. Therefore, we used 2-DG to observe its effect on pulmonary inflammation and fibrosis in a silicosis mouse model. Furthermore, in vitro cell experiments were conducted to explore the specific mechanisms of HIF-1α. Our study found that 2-DG down-regulated HIF-1α levels in alveolar macrophages induced by silica exposure and reduced the interleukin-1ß (IL-1ß) level in pulmonary inflammation. Additionally, 2-DG reduced silica-induced pulmonary fibrosis. From these findings, we hypothesize that 2-DG reduced glucose transporter 1 (GLUT1) expression by inhibiting glycolysis, which inhibits the expression of HIF-1α and ultimately reduces transcription of the inflammatory cytokine, IL-1ß, thus alleviating lung damage. Therefore, we elucidated the important regulatory role of HIF-1α in an experimental silicosis model and the potential defense mechanisms of 2-DG. These results provide a possible effective strategy for 2-DG in the treatment of silicosis.

Panax notoginseng preparation plus aspirin versus aspirin alone on platelet aggregation and coagulation in patients with coronary heart disease or ischemic stroke: A meta-analysis of randomized controlled trials.

Purpose: We aimed to evaluate the effects of Panax notoginseng preparations (PNP) containing Panax Notoginseng Saponins (PNS) or Panaxatriol Saponin (PTS) on platelet aggregation and coagulation in the adjuvant treatment of coronary heart disease (CHD) and ischemic stroke (IS). Methods: Randomized controlled trials (RCTs) comparing the combination of PNP and aspirin (ASA) versus ASA alone for CHD or IS were searched in eight databases. Subgroup analysis was performed according to saponin category. When statistical heterogeneity was significant, sensitivity analysis was performed using the leave-one-out approach. Funnel plot, Egger' test, and Begg' test was adopted to detect publication bias. Results: Twenty RCTs involving 2216 patients were analyzed. Compared with ASA alone, PNP plus ASA had a stronger inhibitory effect on in PAgR [PNS, WMD = -6.10 (-7.25, -4.95), p < 0.00001; PTS, WMD = -3.53 (-4.68, -2.38), p < 0.00001]; PNS plus ASA better reduced FIB [WMD = -0.43 (-0.49, -0.36)] and DD [WMD = -0.59 (-0.67, -0.51), p < 0.00001], while PLT (p = 0.07) and PT (p = 0.34) were not significantly different; PTS plus ASA better prolonged PT [WMD = 1.90 (1.47, 2.32), p < 0.00001] and PT-INR [WMD = 0.22 (0.11, 0.32), p < 0.0001], whereas no significant difference in DD (p = 0.1) and bleeding-related events (positive fecal occult blood, p = 0.96; upper gastrointestinal bleeding, p = 0.67; subcutaneous hemorrhage, p = 0.51; bulbar conjunctival hemorrhage, p = 0.51; hematuria, p = 0.58). There was no significant difference between PNP plus ASA and ASA alone in terms of gastrointestinal side effect (PNS, p = 0.65; PTS, p = 0.56) and urticaria (PNS, p = 0.57; PTS, p = 0.55). Conclusion: PNP combined with ASA might produce stronger antiplatelet aggregation and anticoagulation effects without increasing bleeding risk, gastrointestinal side effects, and urticaria compared with ASA alone. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42022339234.

Impact of Prasugrel and Ticagrelor on Platelet Reactivity in Patients With Acute Coronary Syndrome: A Meta-Analysis.

Background: This meta-analysis mainly aimed to compare the impact of prasugrel and ticagrelor on platelet reactivity (PR) in patients with acute coronary syndrome (ACS). Methods: We searched four electronic databases to identify randomized controlled trials and cohort studies comparing the impact of prasugrel and ticagrelor on PR in patients with ACS. We performed group analyses according to three detection methods, drug dose [loading dose (LD) and maintenance dose (MTD)] and LD effect time, and assessed the robustness of the results through sensitivity analysis. Results: Twenty-five studies with 5,098 patients were eligible. After LD, the incidence of high on-treatment platelet reactivity (HTPR) of ticagrelor was significantly lower than that of prasugrel within 6-18 h based on vasodilator-stimulated phosphoprotein (VASP) test [RR = 0.25 (0.07, 0.85), P = 0.03], there was no significant difference between ticagrelor and prasugrel in the following results: platelets inhibitory effect within 24-48 h based on VerifyNow P2Y12 (VN) assay (P = 0.11) and VASP test (P = 0.20), and the incidence of HTPR within 2-6 h based on VN assay (P = 0.57) and within 24-48 h based on VN assay (P = 0.46) and VASP test (P = 0.72), the incidence of low on-treatment platelet reactivity (LTPR) within 6-18 h based on VASP test (P = 0.46) and 48 h based on VN assay (P = 0.97) and VASP test (P = 0.73). After MTD, the platelet inhibitory effect of ticagrelor was stronger than that of prasugrel based on VN assay [WMD = -41.64 (-47.16, -36.11), P < 0.00001]and VASP test [WMD = -9.10 (-13.88, -4.32), P = 0.0002], the incidence of HTPR of ticagrelor was significantly lower than that of prasugrel based on VN assay [RR = 0.05 (0.02, 0.16), P < 0.00001], the incidence of LTPR of ticagrelor was significantly higher than prasugrel based on VN assay [RR = 6.54 (4.21, 10.14), P < 0.00001] and VASP test [RR = 2.65 (1.78, 3.96), P < 0.00001], the results of Multiple Electrode Aggregometry (MEA) test was inconsistent with the other two detection methods in platelet inhibitory effect and the incidence of HTPR and LTPR. There was no significant difference between ticagrelor and prasugrel in the following clinical outcomes: all-cause death (P = 0.86), cardiovascular death (P = 0.49), myocardial infarction (P = 0.67), stroke (P = 0.51), target vessel revascularization (P = 0.51), stent thrombosis (P = 0.90), TIMI major bleeding (P = 0.86) and bleeding BARC type ≥ 2 (P = 0.77). The risk of bleeding BARC type 1 of ticagrelor was significantly higher than prasugrel [RR = 1.44 (1.03, 2.02), P = 0.03]. Conclusions: Compared with prasugrel, ticagrelor might have a stronger platelet inhibition effect, with a lower incidence of HTPR and a higher incidence of LTPR and bleeding BARC type 1, while there might be no significant difference in the risk of thrombosis/ischemic, bleeding BARC Type ≥ 2 and TIMI major bleeding. A higher incidence of LTPR might indicate a higher risk of bleeding BARC type 1. The results of VN assay were consistent with that of VASP test, and not with the MEA test. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022304205, identifier: CRD42022304205.

Effects of Three Traditional Chinese Fitness Exercises Combined with Antihypertensive Drugs on Patients with Essential Hypertension: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To compare the efficacy of three different traditional Chinese exercises (Tai Chi, Baduanjin, and Wuqinxi) combined with antihypertensive drugs (AHD) on patients with essential hypertension (EH). METHOD: Eight electronic databases were searched to identify randomized controlled trials (RCTs) comparing the effects of traditional Chinese fitness exercises combined with AHD and AHD alone. The analysis mainly consists of network meta-analysis (NMA) and pairwise meta-analysis. The Cochrane assessment tool was adopted to assess the risk of bias of included literatures. This study used STATA/SE 15.1 (StataCorp, 2017), R software (version 4.0.1), and Cochrane's Review Manager software (version 5.4) to conduct data analysis and figures generation. RESULTS: A total of 30 RCTs were included in this study, of which 16 evaluated Tai Chi plus AHD versus AHD, 11 evaluated Baduanjin plus AHD versus AHD, and 3 evaluated Wuqinxi plus AHD versus AHD. No RCT compared directly among the three traditional Chinese fitness exercises. Pairwise meta-analysis showed that Tai Chi plus AHD was significantly superior to AHD alone in reducing systolic blood pressure (SBP) and diastolic blood pressure (DBP). BDJ plus AHD was statistically superior to AHD alone in reducing SBP, DBP, and endothelin (ET) and increasing nitric oxide (NO). NMA results indicated that Tai Chi plus AHD (WMD -12.42 mmHg, 95% CI: -15.29 to -9.55) and Baduanjin plus AHD (WMD -7.03 mmHg, 95% CI: -9.80 to -4.26) were superior to AHD, and Tai Chi was more effective than other traditional exercises in lowering SBP, Tai Chi plus AHD (WMD -7.56 mmHg, 95% CI: -10.15 to -4.96) and Baduanjin plus AHD (WMD -4.51 mmHg, 95% CI: -7.38 to -1.65) were superior to AHD in reducing DBP, Baduanjin plus AHD (WMD 4.26 µmol/L, 95%CI: 2.68 to 5.83) was statistically superior to AHD in increasing NO, and Tai Chi plus AHD (WMD -7.64 pg/ml, 95% CI: -10.46 to -4.83) and Baduanjin plus AHD (WMD -9.23 pg/ml, 95% CI: -10.85 to -7.61) were superior to AHD in lowering ET. CONCLUSION: Compared with AHD alone, both Tai Chi plus AHD and Baduanjin plus AHD showed significant benefit in regulating SBP, DBP, and ET. Among the three traditional Chinese fitness exercises, Tai Chi may be the best as an adjunctive therapy for SBP reduction. These findings provided evidence for the therapeutic benefit of either Tai Chi or Baduanjin exercise as an adjunct therapy for patients with EH. Limited by the methodological quality and quantity of included studies, results need to be interpreted with caution, and it is necessary to carry out further high-quality RCTs on traditional Chinese fitness exercise-assisted treatment of EH in the future.

Songling Xuemaikang capsules for patients with low-to-medium risk hypertension: study protocol for a randomized controlled trial.

BACKGROUND: Hypertension is a major risk factor for cardio-cerebrovascular disease. Songling Xuemaikang capsules (SXC), a formulation of Chinese herbal patent medicine, has been used as a complementary medicine with conventional western medicine to treat patients with hypertension since 1994 in mainland China. However, the efficacy of treatment with SXC alone against hypertension remains unclear. METHODS/DESIGN: This is a multicenter, placebo-controlled, double-blinded, randomized controlled clinical trial. A total of 570 patients with low-to-medium risk hypertension are randomized in a 1:1 ratio to receive SXC or placebo three times daily for eight weeks. The primary outcomes are 24-h average systolic blood pressure and average diastolic blood pressure. The secondary outcomes are daytime average blood pressure, night-time average blood pressure, fluctuation of blood pressure, hypertension control rate, traditional Chinese medicine (TCM) syndrome scores, and quality-of-life scores. DISCUSSION: This is the first multicenter trial conducted to evaluate the efficacy and safety of TCM in patients with low-to-medium risk hypertension. Our study will provide evidence-based results of a complementary preventive measure for hypertension. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IPR-17011383 . Registered on 12 May 2017.

Relationship between two blood stasis syndromes and inflammatory factors in patients with acute coronary syndrome.

OBJECTIVE: To investigate the relationship between inflammatory factors and two Chinese medicine (CM) syndrome types of qi stagnation and blood stasis (QSBS) and qi deficiency and blood stasis (QDBS) in patients with acute coronary syndrome (ACS). METHODS: Sixty subjects with ACS, whose pathogenesis changes belongs to qi disturbance blood stasis syndrome, were divided into 2 groups: 30 in the QSBS group and 30 in the QDBS group. The comparative analysis on them was carried out through comparing general information, coronary angiography and inflammatory factors including intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40) and lipoprotein-associated phospholipase A2 (Lp-PLA2). RESULTS: Compared with the QSBS group, Lp-PLA2 and YKL-40 levels in the QDBS group showed no-significant difference (P>0.05); ICAM-1 was significantly higher in the QDBS group than in the QSBS group in the pathological processes of qi disturbance and blood stasis syndrome of ACS (P<0.05). CONCLUSIONS: Inflammatory factor ICAM-1 may be an objective basis for syndrome typing of QSBS and QDBS, which provides a research direction for standardization research of CM syndrome types.

[Development and Quality Evaluation of Evidence-based Clinical Practice Guidelines of Chinese Medicine].

More attentions have been paid to the development of evidence-based clinical practice guidelines (ECPGs) of Chinese medicine (CM). International guideline evaluation instruments such as Appraisal of Guidelines for Research and Evaluation (AGREE I) has been gradually applied in ECPGs quality evaluation of CM. Nowadays, there are some certain methodological defects in partial ECPGs of Chinese medicine, with relatively low applicability and slowly update. It is suggested to establish technical specifications of CM-ECPGs in accordance with the characteristics of CM and international general specification, strengthen the quality evaluation of CM-ECPGs, attach great importance to the regularly update as well as popularization and application of CM-ECPGs.

Correlation between Platelet Gelsolin and Platelet Activation Level in Acute Myocardial Infarction Rats and Intervention Effect of Effective Components of Chuanxiong Rhizome and Red Peony Root.

The biological role of platelet gelsolin in platelet activation of acute myocardial infarction is not defined. In order to provide a potential new antiplatelet target for Chinese medicine and to elucidate the contribution of Xiongshao capsule, the effective components of Chuanxiong rhizome and red peony root, in this study, we randomly allocated Sprague Dawley rats to left anterior descending coronary artery ligation or sham surgery and different drug prophylaxis as control. We found that gelsolin is highly expressed in platelet rich plasma and lowly expressed in platelet poor plasma, accompanied by the high platelet activation level in model rats; plasma actin filaments and mean fluorescence intensity (MFI) of platelet calcium ion increased and plasma vitamin D binding protein decreased in model rats. Xiongshao capsule could inhibit the gelsolin expression in platelet rich plasma and ischemic heart tissue simultaneously and reduce the level of plasma F-actin and MFI of platelet calcium ion. Our study concludes that platelet gelsolin is an important contributor to platelet activation, and platelet gelsolin inhibition may form a novel target for antiplatelet therapy. Xiongshao capsule may be a promising Chinese medicine drug for antiplatelet and aspirin-like cardioprotection effect.

Ischemic postconditioning through percutaneous transluminal coronary angioplasty in pigs: roles of PI3K activation.

BACKGROUND: Ischemic postconditioning (IPOC) has been suggested to reduce ischemic reperfusion injury. It remains unclear whether the activation of phosphatidylinositol 3 kinase (PI3K)/Akt is a causal mechanism in the cardioprotection afforded by IPOC, which was examined in the model of percutaneous transluminal coronary angioplasty (PTCA) minipigs. METHODS AND RESULTS: Minipigs underwent 45-min occlusion of the left anterior descending artery and 24-h reperfusion by PTCA. Postconditioning was elicited by three cycles of 30-s reperfusion followed by 30-s ischemia at the onset of reperfusion. Infarct size was determined by triphenyl tetrazolium chloride staining after 24-h reperfusion, and mRNA and protein expression levels of PI3K were ascertained by reverse transcriptase-PCR and western-blot analysis in biopsies. Infarct size was significantly reduced and myocardial PI3K (Akt and GSK-3ß) phosphorylation was significantly increased with IPOC treatment compared with ischemic reperfusion. The administration of the PI3K inhibitor wortmannin (30 µg/kg) attenuated the protection of IPOC in the infarct size and decreased the expression of Akt and GSK-3ß phosphorylation compared with IPOC. IPOC had no impact on mRNA expression of AKT and GSK-3ß. CONCLUSION: Our findings show that IPOC is capable of protecting the myocardium against IR injury in the PTCA minipig model. The PI3K/Akt-signaling pathway is involved in the cardioprotective effect of IPOC.

Effect of chinese herbal drug-containing serum for activating-blood and dispelling-toxin on ox-LDL-induced inflammatory factors' expression in endothelial cells.

OBJECTIVE: To investigate the effects of drug-containing serum of Chinese herbal compound, Xiongshao Capsule (, XS, for activating-blood) and Huanglian Capsule (, HL, for dispellingtoxin) on the oxidized low-density lipoprotein (ox-LDL)-induced inflammatory factors in human umbilical vein endothelial cells (HUVECs). METHODS: Thirty-two rats were randomly divided into four groups: the blank control group treated with distilled water, the positive control group treated with simvastatin (1.8 mg/kg), the test group I treated with Chinese herbal compound of XS (0.135 g/kg), and the test group II treated with Chinese herbal compound of XS (0.135 g/kg) and HL (0.135 g/kg). All the treatments were administered for 7 successive days by gastrogavage. Rats' blood serum was harvested 1 h after the last administration to prepare respective drugcontaining serum. HUVECs were exposed to ox-LDL (100 µg/mL) to induce cell injury model and incubated with corresponding drug-containing serum for 24 h. Untreated HUVECs were set for blank control. Levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and soluble intercellular adhesion molecule-1 (sICAM-1) in supernatant of cultured HUVECs were determined by enzyme-linked immunosorbent assay (ELISA). HUVEC surface expressions of ICAM-1 and E-selectin were determined by flow cytometry. RESULTS: Levels of IL-6, TNF-α, and sICAM-1 in the supernatant of HUVECs as well as the cell surface expressions of ICAM-1 and E-selectin significantly increased after 24-h ox-LDL stimulation (P<0.01), while the abnormal elevations, except sICAM-1 in the test group I, were all reduced in the treated groups (the positive control and the two test groups) significantly (P<0.01 or P<0.05). Besides, the effect in the test group II seemed somewhat higher than that in the test group I but with no statistical significance (P>0.05). CONCLUSION: Drug-containing serum of XS plus HL has a certain inhibitory effect on the vascular endothelial inflammation response induced by ox-LDL.

Dynamic expression of the main related indicators of thrombosis, inflammatory reaction and tissue damage in a rat model of myocardial infarction.

In this study, the dynamic expression of granule membrane protein-140 (GMP-140), tissue-type plasminogen activator (t-PA), high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 was observed in a rat model of myocardial infarction. Out of 276 Wistar rats, 6 were randomly selected as the control group, and the rest were randomly divided into 18 groups, with 15 rats in each group. The left coronary artery was ligated in 9 groups to establish the myocardial infarction model, and the remaining 9 groups served as the sham-operated groups without ligature. Of the surviving rats, 6 were randomly selected from each myocardial infarction group and sham-operated group, respectively, at 6, 12, 18, 24 and 36 h, and at 2, 3, 5 and 7 days after successful modeling. Serum levels of GMP-140, t-PA, hs-CRP, IL-6, MMP-9 and TIMP-1 were then detected using an enzyme-linked immunoassay. The results revealed that, after successful modeling, the serum levels of GMP-140 and MMP-9 continually increased, reaching the first peak at 18 h and the maximum peak on day 2. Levels then decreased slightly, but remained higher than those of the control group (p<0.05). The serum levels of hs-CRP and IL-6 increased, reached a peak at 18 h, and then decreased slightly, but were still significantly higher than those of the control group (p<0.05). The serum level of t-PA decreased significantly (p<0.05) and was restored to baseline by day 5. The serum level of TIMP-1 started to decrease as of 24 h, but was maintained until day 7 (p<0.05). In conclusion, in a rat model of myocardial infarction, the thrombosis, inflammatory reaction and tissue damage-related indicators GMP-140, hs-CRP, IL-6 and MMP-9 increased significantly, while t-PA and TIMP-1 decreased dynamically. Based on the dynamic changes of each indicator, the optimal intervention time may be determined.

[Effects of Chinese herbal drug-containing serum on oxidative damage and apoptosis of umbilical vein endothelial cells induced by oxidized low-density lipoprotein].

OBJECTIVE: To investigate the effects of Chinese herbal drug-containing serum, prepared by administration of Chinese herbal medicine for activating blood (Xiongshao Capsule, XS) or for activating blood and detoxifying (Xiongshao Capsule plus Huanglian Capsule, XSHL) in rats, on cell viability, oxidative damage and apoptosis of human umbilical vein endothelial cells (HUVECs) induced by oxidized low-density lipoprotein (ox-LDL). METHODS: Thirty-two rats were randomly divided into 4 groups: control group, positive control group (simvastatin 1.8 mg/kg), activating blood (XS, 0.135 g/kg) group, and activating blood and detoxifying (XS Capsule 0.135 g/kg and Huanglian Capsule 0.135 g/kg, XSHL) group. Corresponding drugs were continuously administered to the rats for 7 days and then drug-containing serum was harvested 1 hour after the last administration. HUVECs isolated from newborn children by collagenase digestion were stimulated by ox-LDL (100 µg/mL) [corrected] and incubated with corresponding drug-containing serum for 24 hours. Untreated HUVECs were also used as a normal control. The morphology and structure of HUVECs were observed by an inverted microscope. Cell viability was measured by methyl thiazolyl tetrazolium method, and cell membrane damage was determined by lactate dehydrogenase (LDH) leakage. Activity of superoxide dismutase (SOD) was examined by spectrophotometry, and content of malondialdehyde (MDA) in the cell lysate was examined by thiobarbituric acid assay. HUVECs were stained with Annexin V-fluorescein isothiocyanate and propidium iodide and analyzed on a flow cytometry to determine apoptosis. RESULTS: Compared with the normal HUVECs, the cell viability and the activity of SOD were significantly decreased while the content of MDA and apoptosis rate were significantly increased after 24-hour ox-LDL stimulation (P<0.01, P<0.05). Simvastatin-, XS-, and XSHL-containing serum significantly promoted the ox-LDL-stimulated HUVEC viability and inhibited early apoptosis (P<0.01, P<0.05), while had no significant effect on LDH leakage. Simvastatin-containing serum and XS-containing serum also showed significant decrease in MDA content and increase in SOD activity, while XSHL-containing serum showed no significant effects. There was no significant difference between the XS-containing serum group and the XSHL-containing serum group. CONCLUSION: Both sera containing XSHL and XS show protective action against the oxidative damage and apoptosis of HUVECs induced by ox-LDL.

[Translational medicine and its application in research & development of integrative medicine].

The background, concept and status quo of translational medicine at home and abroad were introduced systematically in this review, and the application mode of translational medicine in the research and development of Chinese medicine (CM) was analyzed. Targeting the characteristics of CM and the changes in the spectrum of diseases in China, some suggestions were made to strengthen the translational research in CM and integrative medicine.

[Screening, identification and analysis of platelet differential functional proteins in patients with coronary heart disease of blood-stasis pattern].

OBJECTIVE: To seek the key platelet functional proteins (PFPs) for the occurrence of blood-stasis pattern (BP) in patients with coronary heart disease (CHD). METHODS: Peripheral blood platelet protein of 22 patients and 24 healthy person (for control) were extracted respectively in 4 batches for carrying 4 times of the test out. Differential PFPs in samples were screened out by two-dimensional fluorescence difference gel electrophoresis, and identified with matrix-assisted laser desorption/ionization-time of flight mass spectrometry; then the identified proteins were further authenticated by Western-blotting. RESULTS: Thirteen differential PFPs were screened out, and among them the 7 identified by spectrometry were: isoform 1 of integrin alpha- II b, isoform 2 of integrin alpha- II b, actin-cytoplasmic 1, actin-cytoplasmic 2, cDNA FLJ52842, cDNA FLJ55253, and cDNA FLJ43573 fis. Among them isoform 2 of integrin alpha- II b (CD41) and actin-cytoplasmic 2 (Acting) were authenticated successfully. CONCLUSION: CD41 and acting are the possible marker proteins, and the other PFPs might play crucial roles in the occurrence and development of BSS in CHD.

Effect of Chinese herbal medicine for activating blood circulation and detoxifying on expression of inflammatory reaction and tissue damage related factors in experimental carotid artery thrombosis rats.

OBJECTIVE: To observe the pharmaceutical effect of Chinese drugs for activating blood circulation (Xiongshao Capsule, XSC, ) and for activating blood circulation and detoxification (Xiongshao Capsule and Huanglian Capsule, XSHLC, ) in terms of the indices of thrombosis, inflammatory reaction and tissue damage related factors in experimental carotid artery thrombosis rats. METHODS: Fifty Wistar rats were randomly divided into the sham operation group, the model group, the Simvastatin group (SG), the activating blood circulation (ABC) group, and the activating blood circulation and detoxifying (ABCD) group, with 10 rats in each group. Simvastatin (1.8 mg/kg), XSC (0.135 g/kg) and XSHLC (0.135 g/kg) were administered to Simvastatin, ABC and ABCD group by gastrogavage, and an equal volume of normal saline was given to the sham operation group and the model group. After 2 weeks of successive medication, the rats in the model and all drug therapy groups were made into experimental carotid artery thrombosis model. The serum levels of matrix metalloproteinases (MMP-9), tissue inhibitors to metalloproteinase (TIMP-1), granule membrane protein-140 (GMP-140), tissue-type plasminogen activator (t-PA), high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) were detected with enzyme-linked immunoassay 24 h later. RESULTS: Compared with the model group, the levels of serum GMP-140, hs-CRP, IL-6 and MMP-9 were significantly decreased, and the level of t-PA was significantly increased in the ABC and ABCD group ( P<0.05), while the level of serum hs-CRP in ABCD group decreased significantly compared with that in the ABC group (P<0.05). CONCLUSIONS: Chinese drugs both for activating blood circulation and for activating blood circulation and detoxifying have good effects on regulating indices of thrombosis, inflammatory reaction and tissue damage in experimental carotid artery thrombosis rats. The effect of activating blood circulation and detoxifying drugs on regulating the level of serum hs-CRP is superior to that of activating blood circulation drug alone.

Effects of active components of Red Paeonia and Rhizoma chuanxiong on angiogenesis in atherosclerosis plaque in rabbits.

OBJECTIVE: To investigate the effects and mechanism of the active components of Red Paeonia and Rhizoma chuanxiong (Xiongshao Capsule, XSC) on angiogenesis in atherosclerosis plaque in rabbits. METHODS: Fifty New Zealand rabbits were randomly divided into the normal group, the model group, and the three medicated groups treated respectively with Simvastatin (2.5 mg/kg per day), low-dose (0.24 g/kg per day) and high-dose (0.48 g/kg per day) XSC, 10 in each group. Rabbits in the normal group were fed with regular diet. To those in the other four groups, high fat diet was given, and a balloon angioplasty was performed two weeks later to establish abdominal aortic atherosclerosis model. Then, the model rabbits were fed continuously with high fat diet, and to those in the medicated groups, the testing drugs were added in the forage correspondingly for 6 successive weeks. Levels of blood lipids were measured at the end of the experiment. Meantime, serum levels of high sensitivity C-reactive protein (hsCRP) and tumor necrosis factor alpha (TNF-alpha) were detected with enzyme-linked immunoassay; the plaque area (PA), cross-sectional vascular area (CVA) and correcting plaque area (PA/CVA) were determined quantitatively using imaging software; and the protein expression of vascular endothelial growth factor (VEGF) and factor VIII related antigen (FVIIIRAg) in plaque was detected using immunohistochemical method. RESULTS: As compared with the model group, the content of total cholesterol (TC) in the three medicated groups, and contents of triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) in the Simvastatin group were lower to various extents (P<0.05, P<0.01). The serum level of hsCRP in all modeled rabbits was higher than that in the normal group, but in the three treated groups it was significantly lower than that in the model group (P<0.05, P<0.01). Expressions of VEGF and FVIIIRAg, as well as PA/CVA in the three medicated groups were significantly lower than those in the model control group (P<0.05, P<0.01). CONCLUSION: The active components of Red Paeonia and Rhizoma chuanxiong have definite effects in delaying the genesis and development of atherosclerosis, its mechanism might be related with the inhibition on angiogenesis in plaque, and also with its actions of lipo-metabolism regulation and anti-inflammation.