丹皮酚对大鼠心肌缺血再灌注损伤中高迁移率族蛋白B1和白细胞介素1β及心肌凋亡的影响

Effect of paeonol on expression of HMGB1,IL-1β and apoptosis of cardiomyocytes in rats after myocardial I/R injury

目的探讨丹皮酚对大鼠心肌缺血再灌注损伤保护中高迁移率族蛋白B1(HMGB1)、白细胞介素1β(IL-1β)表达及心肌凋亡的影响。方法选择成年SPF级雄性SD大鼠52只,随机分为假手术组、丹皮酚低剂量组、丹皮酚高剂量组和缺血再灌注组,每组13只。丹皮酚低剂量组、丹皮酚高剂量组于术前15d腹腔分别注射丹皮酚15、30mg/kg,1次/d。再灌注2h取血清,采用ELISA法测定IL-1β水平;TTC染色法测定心肌梗死面积,免疫组织化学法测定心肌组织中HMGB1、Bcl-2和Bax蛋白表达水平。结果与缺血再灌注组比较,丹皮酚低剂量组、丹皮酚高剂量组心肌梗死面积明显减小[(31.04±2.93)%、(27.97±2.84)%vs (37.23±3.62)%,P<0.01]。与假手术组比较,缺血再灌注组、丹皮酚低剂量组和丹皮酚高剂量组IL-1β和HMGB1表达明显升高(P<0.01)。与缺血再灌注组比较,丹皮酚低剂量组和丹皮酚高剂量组IL-1β和HMGB1表达明显降低(P<0.01)。与缺血再灌注组比较,丹皮酚低剂量组和丹皮酚高剂量组Bcl-2表达明显升高,Bax表达明显降低(P<0.05)。结论丹皮酚预处理可通过减少心肌凋亡和炎性反应,实现对心肌缺血再灌注损伤的保护作用。

Objective To study the effect of paeonol onexpression of HMGB1 and IL-1β and apoptosis of cardiomyocytes in rats after myocardial I/R injury.Methods Fifty-two adult SPF male SD rats were randomly divided into sham operation group,low-dose paeonol group,high dose paeonol group,and I/R injury group(13 in each group).The rats in low-dose paeonol group and high dose paeonol group received intraperitoneal paeonol injection before operation(15.30 mg/kg,once a day).Serum samples were taken at 2 h after reperfusion.Serum IL-1β level was measured by ELISA,myocardial infarction size was measured with TTC staining,expressions of HMGB1,Bcl-2 and Bax proteins in myocardial tissue were detected with immunohistochemical staining.Results The myocardial infarction size was significantly smaller in low-dose paeonol group and high dose paeonol group than in I/R injury group(31.04%±2.93%,27.97%±2.84 vs 37.23%±3.62%, P<0.01).The expression levels of IL-1β and HMGB1 were significantly higher in I/R injury group,low-dose paeonol group and high-dose paeonol group than in sham operation group and were significantly lower in low-dose paeonol group and high-dose paeonol group than in I/R injury group(P<0.01).The expression level of IL-1β was significantly higher while that of Bax protein was significantly lower in low-dose paeonol group and high-dose paeonol group than in in I/R injury group(P<0.05).Conclusion Paeonol preconditioning can reduce apoptosis of cardiomyocytes, and can thus prevent myocardial I/R injury.