Shexiang Baoxin Pill Regulates Intimal Hyperplasia, Migration, and Apoptosis after Platelet-Derived Growth Factor-BB-Stimulation of Vascular Smooth Muscle Cells via miR-451 / 中国结合医学杂志

OBJECTIVE@#To investigate the regulatory roles of Shexiang Baoxin Pill (SXBXW) in neointimal formation and vascular smooth muscle cells (VSMCs) invasion and apoptosis as well as the potential molecular mechanisms using cultured VSMCs model of vascular injury (platelet-derived growth factor (PDGF)-BB-stimulated) in vitro.@*METHODS@#VSMCs were randomly assigned to 5 groups: blank, PDGF-BB (20 ng/mL+ 0.1% DMSO), SXBXW-L (PDGF-BB 20 ng/mL + SXBXW low dose 0.625 g/L), SXBXW-M (PDGF-BB 20 ng/mL + SXBXW medium dose 1.25 g/L) and SXBXW-H (PDGF-BB 20 ng/mL+ SXBXW high dose 2.5 g/L) group. Cell proliferation was assessed using cell counting kit-8 (CCK-8) assay and bromodeoxyuridine (BrdU) incorporation assay, the migration effects were detected by Transwell assay, cell apoptosis rate was measured by the Annexin V/propidium iodide (PI) apoptosis kit. The markers of contractile phenotype of VSMCs were detected with immunofluorescent staining. To validate the effects of miR-451 in regulating proliferation, migration and apoptosis treated with SXBXW, miR-451 overexpression experiments were performed, the VSMCs were exposed to PDGF-BB 20 ng/mL + 0.1% DMSO and later divided into 4 groups: mimic-NC (multiplicity of infection, MOI=50), SXBXW (1.25 g/L) + mimic-NC, mimic-miR451 (MOI=50), and SXBXW (1.25 g/L) + mimic-miR451, and alterations of proteins related to the miR-451 pathway were analyzed using Western blot.@*RESULTS@#PDGF-BB induced VSMCs injury causes acceleration of proliferation and migration. SXBXW inhibited phenotypic switching, proliferation and migration and promoted cell apoptosis in PDGF-BB-induced VSMCs. In addition, miR-451 was shown to be down-regulated in the VSMCs following PDGF-BB stimulation. SXBXW treatment enhanced the expression of miR-451 in PDGF-BB-induced VSMCs (P<0.05). Compared with SXBXW + mimic-NC and mimic-miR451 groups, the expression of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (Ywhaz) and p53 was further reduced in SXBXW + mimic-miR451 group, while activating transcription factor 2 (ATF2) was increased in VSMCs (P<0.05).@*CONCLUSION@#SXBXW regulated proliferation, migration and apoptosis via activation of miR-451 through ATF2, p53 and Ywhaz in PDGF-BB-stimulated VSMCs.

Meta analysis on efficacy of Compound Danshen Dropping Pills in treating angina based on syndrome differentiation / 中草药

Objective: To evaluate the efficacy and safety of the combination therapy of Compound Danshen Dropping Pills and conventional chemical drugs in the treatment of the angina by Meta-analysis. Methods: Databases including CNKI, WanFang, CBM, VIP, PubMed, and Cochrane Library were searched to collect qualified researches, and the quality of articles was evaluated according to Cochrane Handbook. Meta-analysis including subgroup analysis was performed by using Stata 13.1 and RevMan 5.3 software. All these methods were used to systematically evaluate the safety and clinical efficacy of Compound Danshen Dropping Pills in the treatment of angina pectoris under two circumstances (with or without syndrome differentiation). Results: A total of 39 studies involving 3 941 patients were studied, including 1 991 patients in the experimental group and 1 950 in the control group. The results of Meta analysis showed that: the clinical efficacy [RR = 1.24, 95%CI (1.20, 1.28), P < 0.000 01], ECG efficacy [RR = 1.29, 95%CI (1.21, 1.37), P < 0.000 01], angina attack frequency [WMD = -1.82, 95%CI (-3.28, -0.36), P = 0.01], duration of angina attack [WMD = -2.09, 95%CI (-2.67, -1.50), P < 0.000 01], hs-CRP [WMD = -2.63, 95%CI (-4.39, -0.86), P = 0.003], ET [WMD = -16.22, 95%CI (-19.37, -13.06), P < 0.000 01], platelet aggregation [WMD=-7.46, 95%CI (-11.15, -3.78), P < 0.000 1], GMP-140 [WMD=-5.64, 95%CI (-6.88, -4.39), P < 0.000 01] and fibrinogen [WMD = -0.73, 95%CI (-1.00, -0.46), P < 0.000 01] of routine western medicine treatment combine with Compound Danshen Dripping Pills group had significant difference compared with the control group; In terms of clinical efficacy, the combination effect of dialectical medication group and non dialectical medication group had no significant difference (P = 0.55, I2 = 0). A total of 15 studies described adverse reactions, with 43 cases in the experimental group and 65 cases in the control group. There was no significant publication bias on funnel plot and Egger's test. Conclusion: It is safe and effective to use Compound Danshen Dropping Pills in patients with coronary heart disease and angina, which can further improve the clinical effect compared with the simple routine treatment. There is no significant difference between the therapeutic effect of Compound Danshen Dropping Pills and that of non-syndrome differentiation. However, these conclusions still need to be verified with more high-quality and large-sample literature.