制大黄-川芎“药对”抑制造影剂肾病大鼠肾小管上皮细胞凋亡信号通路的机制研究  

Research on Radix et Rhizoma Rhei-Rhizoma Ligustici Chuanxiong restraining renal tubular epithelial cell apoptosis in contrast-induced nephropathy rats

作　　者：龚学忠[1] 王骞[1] 符丹[1] 汤晓春[1] 王跃荣[2] 王国华[3] 陆华懿[1] 

机构地区：[1]上海中医药大学附属市中医医院肾内科,上海200071 [2]上海中医药大学附属市中医医院检验科,上海200071 [3]上海中医药大学附属市中医医院实验中心,上海200071

出　　处：《上海中医药杂志》2013年第3期69-71,共3页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金青年项目(81001509);上海市教委创新项目(10YZ59)

摘　　要：目的研究制大黄-川芎"药对"抑制造影剂肾病(CIN)大鼠肾小管上皮细胞凋亡信号通路的机制。方法将32只雄性SD大鼠分为正常组(A组)、模型组(B组)、药对组(C组)、N-乙酰半胱氨酸(NAC)组(D组)。C组于造模前7天每日灌胃"药对"水煎液,D组造模前3天每日腹腔注射NAC(150μg/g)。B、C、D 3组按照文献方法制备CIN模型。造模后24 h处死大鼠,测定血清肌酐(Scr)、尿素氮(BUN);HE染色观察肾脏病理改变,Western印迹检测肾组织p-p38 MAPK、Bcl-2及Bax表达。结果与A组比较,B、C、D组大鼠血清肌酐、尿素氮均明显升高(P<0.05,P<0.01),出现肾间质水肿、肾小管上皮细胞胞浆空泡样变,p-p38 MAPK、Bax蛋白表达上调,Bcl-2表达下降。与B组比较,C、D组血清肌酐、尿素氮明显降低(P<0.05),肾脏病理改变显著减轻,p-p38 MAPK、Bax蛋白表达下降,而Bcl-2表达增加(P<0.01)。结论 p38 MAPK通路活化参与了CIN大鼠急性肾损伤过程,且制大黄-川芎"药对"能通过抑制该通路活化保护CIN大鼠肾功能。Objective To research the mechanism of Radix et Rhizoma Rhei-Rhizoma Ligustici Chuanxiong on tubular epithelial cell apoptosis in contrast-induced nephropathy （CIN） rats. Methods Thirty-two male SD rats were divided into four groups ： normal group （ group A）, model group （ group B）, drug pair group （ group C ）, and N-acetyl cysteine （ NAC ） group （ group D）. Rats of group C were given daily intragastric administration with drug pair decoction for 7 days before building model; rats in group D were daily injected intraperitoneally 150mg/kg NAC for 3 days before building model. The CIN models were built in three groups. All rats were killed in 24 h. The Scr and BUN were detected; the pathological changes of kidney were observed by HE staining, and the p-p38MAPK, Bcl-2 and Bax expression were detected by western blotting method. Results Compared with group A, the Scr and BUN in group B, group C and group D were significantly increased （ P 〈0.05, P 〈0. 01 ） ; the interstitial edema and vacuolar degeneration were found in renal tubular epithelial cells. The expressions of p-p38MAPK and Bax proteins were increased, while the Bcl-2 expression was decreased. Compared with group B, the Scr and BUN were decreased in group C and group D （ P 〈 0.05 ） ; the pathological changes were relieved ; the expressions of p-p38 MAPK and Bax protein were significantly decreased, while the Bcl- 2 protein expression was increased （ P 〈 0.01 ）. Conclusion Activation of p38 MAPK pathway plays an important role in pathogenesis of CIN, and Radix et Rhizoma Rhei- Rhizoma Ligustici Chuanxiong can protect the renal function in CIN rats through inhibiting the activation of pathway.

关 键 词：造影剂肾病 肾小管上皮细胞 细胞凋亡 制大黄 川芎 

分 类 号：R285.5[医药卫生—中药学]