灯盏花素对肾损害小鼠肾组织细胞凋亡及相关蛋白的影响

目的:观察灯盏花素对顺铂致小鼠肾损害肾组织细胞凋亡及相关蛋白的影响。方法:将昆明种小鼠随机分为对照组、模型组、灯盏花素25,50 mg.kg-1组。除对照组外,其余各组腹腔注射顺铂8 mg.kg-1制备小鼠肾损害模型,灯盏花素组分别灌胃给药,连续7 d。给药结束后收集小鼠尿液进行尿蛋白(Upr)/尿肌酐(Ucr)及N-乙酰-β-D-氨基葡萄糖苷酶(NAG-U)测定。原位末端标记法(TUNEL)检测小鼠肾脏细胞凋亡状况,免疫组化法检测肾脏相关凋亡蛋白Bax和Bcl-2的表达。结果:模型组小鼠Upr/Ucr及NAG-U较对照组明显升高,肾组织的凋亡指数增加,肾组织细胞凋亡蛋白Bax及Bcl-2表达增强,Bax/Bcl-2比值升高(P<0.05,P<0.01),而2个灯盏花素实验组Upr/Ucr、NAG-U较模型组明显降低(P<0.05,P<0.01),其中灯盏花素50 mg.kg-1小鼠较模型组肾组织细胞凋亡指数、Bax表达、Bax/Bcl-2减少,Bcl-2的表达增强(P<0.05,P<0.01)。结论:Upr/Ucr与NAG-U可作为顺铂肾损害的评估指标。灯盏花素减轻顺铂肾损害的机制可能与增强凋亡相关蛋白Bcl-2的表达,降低Bax表达及Bax/Bcl-2的比值有关。

Effects of Breviscapine on Renal Cell Apoptosis and Expression of Apoptosis-related Proteins in Mice with Cisplatin-induced Nephrotoxicity

Objective: To observe the effects of breviscapine on renal cell apoptosis and expression of apoptosis-related proteins in mice with cisplatin-induced nephrotoxicity. Method: Kunming mice were randomly divided into four groups: control group, model group, breviscapine experimental groups by 25 mg·kg^-1 or 50 mg·kg^-1.Three groups were given a single injection of cis-platinum complexes(CDDP)to establish the model of renal injury(8 mg·kg^-1, ip) except the control group, then the mice in two breviscapine experimental groups were given different dose(25, 50 mg·kg^-1, ig) once a day for seven days.The urine samples were collect for measuring Urine protein(Upr)/Urine creatinine(Ucr) and N-aletyl-beta-D-glucosaminidase(NAG-U).Apoptosis of the renal cells were determined by TUNEL method, also the expression of Bax and Bcl-2 was evaluated by immunohistochemical SP method after the mice were sacrificed. Result: The Upr/Ucr ratio, NAG-U in the model group were higher than those in the control group, but they were significantly lower in two breviscapine groups(P<0.05, P<0.01), also apoptosis index of the renal cells, the expression of Bax and Bcl-2, the Bax/Bcl-2 ratio in the model group were higher than those in the control group.But, in the breviscapine experimental group of 50 mg·kg^-1, apoptosis index was significantly declined(P<0.05, P<0.01), the expression of Bcl-2 was increased, the expression of Bax was declined, the Bax/Bcl-2 ratio was declined compared with those in model group(P<0.05, P<0.01). Conclusion: The Upr/Ucr ratio and NAG-U might be useful for evaluating renal injury induced by CDDP.Breviscapine could suppress renal cell apoptosis induced by CDDP and protect renal from injury by means of increasing the expression of Bcl-2 and declining the expression of Bax and Bax/Bcl-2 ratio.