丹参酮ⅡA注射液联合大黄制剂对急性肾损伤小鼠氧化应激凋亡的影响

Effect of tanshinone ⅡA injection combined with rhubarb preparation on oxidative stress apoptosis in mice with acute kidney injury

目的:探究丹参酮ⅡA注射液联合大黄制剂对小鼠急性肾损伤氧化应激凋亡的影响。方法:选取清洁级,雄性、C57 BL/6小鼠共30只随机分为假手术组(Sham组)、GLP模型组(Model组)和丹参酮ⅡA注射液联合大黄制剂治疗组(TM组),每组各10只,随机选取6只进行实验。利用盲肠结扎穿孔(CLP)构建脓毒症诱导的小鼠急性肾损伤模型。Sham组小鼠自由饮水和饮食3 d。Model组小鼠在造模成功后腹腔注射给予10 ml/kg氯化钠注射液3 d。TM组小鼠造模成功后丹参酮ⅡA注射液10 ml/kg腹腔注射和2 ml/kg的大黄制剂灌肠处理3 d。观察小鼠肾脏形态;检测肾脏细胞凋亡情况;检测血清尿素氮(BUN)、肌酐(Cr)、超氧化物歧化酶(SOD)和丙二醛(MDA)水平。结果:与Sham组小鼠比较,Model组小鼠肾功能明显异常,肾组织细胞凋亡显著,BUN、Cr和MDA含量显著增加(P<0.01),SOD水平显著降低(P<0.01);与Model组小鼠比较,TM组小鼠肾功能得到明显恢复,肾组织细胞凋亡降低,BUN、Cr和MDA含量显著降低(P<0.05或P<0.01),SOD水平显著升高(P<0.01)。结论:丹参酮ⅡA注射液联合大黄制剂对CLP诱导的小鼠急性肾损伤具有保护作用,其可能通过抑制肾脏氧化应激凋亡实现。

Objective:To explore the effect of Tanshinone ⅡA injection combined with rhubarb preparation on oxidative stress apoptosis in mice with acute kidney injury.Methods:A total of 30 SPF-grade male C57 BL/6 mice were randomly divided into sham operation group(sham group),CLP model group(model group),and Tanshinone ⅡA injection combined with rhubarb preparation treatment group(TM group),with 10 mice in each group,and six mice were randomly selected for the experiment.Cecal ligation and perforation(CLP)were used to construct a sepsis-induced acute kidney injury model in mice.The mice in the Sham group were free to drink and eat for three days.Mice in the model group were intraperitoneally injected with 10 ml/kg normal saline for three days after successful model building.After the successful modeling,the mice in the TM group were treated with 10 ml/kg Tanshinone ⅡA injection by intraperitoneal injection and 2 ml/kg rhubarb preparation by enema for three days.The morphology of mouse kidneys was observed by hematoxylin-eosin(HE)staining,and the apoptosis of renal cells were detected by TUNEL staining.The levels of serum urea nitrogen(BUN),creatinine(CR),superoxide dismutase(SOD),and malondialdehyde(MDA)were measured by kits.Results:Compared with the Sham group mice,the model group mice had a significantly abnormal renal function,marked apoptosis in renal tissue,significantly increased BUN,Cr,and MDA content(P<0.01),and significantly decreased SOD level(P<0.01).Compared with the model group,the renal function of the mice in the TM group was significantly restored,the apoptosis of renal cells was reduced,the contents of BUN,Cr,and MDA were significantly reduced(P<0.05 or P<0.01),and the SOD level was significantly increased(P<0.01).Conclusion:Tanshinone ⅡA injection combined with rhubarb preparation has a protective effect on CLP-induced acute kidney injury in mice,which may be achieved by inhibiting renal oxidative stress and apoptosis.