川芎嗪防治大鼠重症急性胰腺炎肾损伤机制研究

Mechanism of Ligustrazine in Preventing and Treating Renal Injury in Rats with Severe Acute Pancreatitis

目的探讨川芎嗪能否通过调节细胞凋亡和炎性介质的释放防治大鼠重症急性胰腺炎(SAP)肾损伤。方法将84只健康雌性大鼠随机均分为对照组、SAP组、川芎嗪组,各28只。对照组开腹后翻动胰腺,即关闭腹腔; SAP组建立SAP动物模型;川芎嗪组在SAP建模成功后注射川芎嗪注射液。分析3组大鼠不同时间点的腹腔积液量、胰腺组织病理评分、炎性介质、肾损伤相关指标及肾脏组织细胞凋亡指数。结果对照组无明显腹腔积液聚积; SAP组术后6,12,24,48 h腹腔积液呈逐渐增多趋势,且显著多于川芎嗪组(P <0. 05);对照组的胰腺组织在各个时间点均无明显病理损害,SAP组术后48 h的水肿、炎症、出血、坏死评分均明显大于川芎嗪组(P <0. 05);SAP组术后6,12,24,48 h的白细胞介素6(IL-6)、白细胞介素10(IL-10)、肿瘤坏死因子-α(TNF-α)均显著高于对照组,且术后24,48 h显著高于川芎嗪组(P <0. 05); SAP组术后6,12,24,48 h的淀粉酶、血清尿素氮(BUN)、血清肌酐(Cr)均显著高于对照组,川芎嗪组术后12,24,48 h的淀粉酶、BUN、Cr显著高于对照组(P <0. 05);川芎嗪组6,12,24,48 h的肾脏组织细胞凋亡指数显著低于SAP组,但明显高于对照组(P <0. 05)。结论川芎嗪能有效改善细胞凋亡与炎性介质的释放,从而保护大鼠的胰腺组织,降低肾损伤。

Objective To investigate whether ligustrazine can protect renal injury in rats with severe acute pancreatitis（SAP） by regulating the cell apoptosis and the release of inflammatory mediators. Methods Totally 84 healthy female rats were randomly divided into the control group,SAP group,ligustrazine group,28 cases in each group. In the control group,laparotomy were performed,the pancrea was flipped only,and then the abdominal cavity was closed. SAP model was made in the SAP group, based on this,the ligustrazine group received Ligustrazine Injection. The amount of ascites, histopathological scores of pancreas, inflammatory mediators, renal injuryrelated indicators,and renal cell apoptosis indexes at different times were analyzed in the three groups. Results The control group had no significant accumulation of ascites. At the postoperative 6,12,24,48 h,the amount of ascites showed a increasing trend in the SAP group,and which was significantly higher than that of the ligustrazine group（P 〈 0. 05）. The pancreatic tissue in the control group had no obvious pathological lesions at all time points. The scores of edema,inflammation,hemorrhage and necrosis at postoperative 48 h in the SAP group were significantly higher than those in the ligustrazine group（P 〈 0.05）. The levels of IL-6,IL- 10 and TNF-α at postoperative 6,12,24,48 h in the SAP group were significantly higher than those in the control group,and the above levels at the postoperative 24,48 h in the SAP group were significantly higher than those in ligustrazine group（P 〈 0.05）. The levels of amylase, BUN and Cr at the postoperative 6,12,24,48 h in the SAP group were significantly higher than those in the control group,and the above levels at the postoperative 12,24,48 h in the ligustrazine group were significantly higher than those in the control group（P 〈 0.05）. The apoptotic index of renal tissue in the ligustrazine group was significantly lower than that in the SAP group at postoperative 6,12, 24,48 h,hut which was significantly higher than that in the control group（P 〈 0.05）. Conclusion Ligustrazine can effectively improve the cell apoptosis and the release of inflammatory mediators,so as to protect rat pancreas tissue and reduce renal injury.