基于PKD1/HDAC7轴研究丹参酚酸B对大鼠缺血心肌组织的保护作用

The protective effect of salvianolic acid B on ischemic myocardium in rats based on PKD1/HDAC7 axis

目的分析丹参酚酸B(salvianolic acid B,SAB)是否通过调控蛋白激酶D1(protein kinase D1,PKD1)/Ⅱa类组蛋白去乙酰化酶7(HDAC7)表达而保护大鼠缺血心肌组织并阐述其作用机制。方法♂Wistar大鼠40只,随机分为假手术(Sham),心梗模型(MI),SAB和CID755673阻断剂(CID)组。结扎左冠状动脉前降支复制MI模型,Sham组不进行结扎操作,其他手术程序和MI组保持一致。14 d实验周期中,大鼠均腹腔注射给药,SAB组:50 mg^-1·kg^-1·d^-1,CID组:50 mg^-1·kg^-1·d^-1 SAB+40μg^-1·kg^-1·d^-1 CID,Sham和MI组:等量生理盐水。应用HE、Masson和TUNEL染色法分析心肌组织的受损情况,免疫荧光、免疫组化和免疫印迹等方法分析心肌组织中PKD1和HDAC7的表达。结果在SAB用药后,MI后的心肌组织受损明显减轻,胶原纤维占比下降,凋亡心肌细胞数量减少,伴随着PKD1和HDAC7的表达上调;注射CID可明显抑制SAB的作用。结论SAB可能通过调控PKD1/HDAC7轴而保护缺血受损的心肌组织。

Aim To analyze whether salvianolic acid B(SAB)protects ischemic myocardium of rats by regulating the expression of protein kinase D1(PKD1)/HDAC7 and to reveal the underlying mechanisms.Methods Forty male Wistar rats were randomly divided into sham group,MI group,SAB group and CID 755673(CID)group.The MI model was reproduced through the hypodesmus of anterior descending branch,while the sham group did not completed the same operation.In the 14 day experimental period,rats were injected intraperitoneally,SAB group:50 mg/kg,CID group:50 mg·kg^-1 SAB+40 mg^-1·kg^-1·d^-1 CID,sham and MI group:equivalent physiological saline.Then the rats were sacrificed,the myocardial injury was assessed through the technique of HE,Masson and TUNEL staining,and the expression of PKD1 and HDAC7 in myocardial tissue was estimated through the means of immunofluorescence,immunohistochemistry and Western blot.Results In SAB group,the damage of myocardial tissue was alleviated,the proportion of collagen fibers decreased,the number of apoptotic cardiomyocytes was reduced,and the expression of PKD1 and HDAC7 was up-regulated.CID could block the effect of SAB.Conclusion SAB might play a role in protecting ischemic myocardium through the regulation of PKD1/HDAC7 axis.