加味黄连阿胶汤对顺铂所致大鼠肾毒性的影响

Effects of Jia Wei HuangLian E-Jiao Tang on Nephrotoxicity Rats Induced by Cisplatin

目的观察加味黄连阿胶汤对顺铂致大鼠肾毒性的治疗作用。方法清洁级雄性SD大鼠60只,随机分正常对照组、模型组、硫代硫酸钠治疗组、加味黄连阿胶汤低剂量治疗组和加味黄连阿胶汤高剂量治疗组,每组12只。其中模型组、硫代硫酸钠治疗组、加味黄连阿胶汤低剂量治疗组和加味黄连阿胶汤高剂量治疗组大鼠尾静脉注射顺铂(用生理盐水配制成1g/L的溶液)5mg/kg体重,1次/周,连续3周。正常对照组用等量生理盐水替代顺铂尾静脉注射。第一次尾静脉注射后,黄连阿胶汤治疗组大鼠给予相应的药物灌胃,正常对照组、模型组给予生理盐水,1次/d,连续8周,灌药体积均为10ml/kg体重;硫代硫酸钠组于尾静脉注射顺铂的同时,注射硫代硫酸钠注射液。实验结束时,剖取肾脏,行过碘酸雪夫(PAS)及免疫组织化学染色。结果模型组大鼠24h尿蛋白(Upro)定量、尿N-乙酰β-D氨基葡萄糖苷酶(NAG)含量均高于正常对照组(P<0.01);硫代硫酸钠组及加味黄连阿胶汤各组24hUpro定量、NAG含量均低于模型组(P<0.05或P<0.01),与正常对照组相比,差别无统计学意义。模型组大鼠肾小管上皮细胞肿胀、空泡变性、坏死、脱落,小管内可见大量的蛋白管型,肾间质有散在的纤维组织增生、大量炎细胞浸润,而加味黄连阿胶汤各组及硫代硫酸钠组大鼠肾脏上述病理改变明显减轻。结论加味黄连阿胶汤能降低顺铂肾毒性大鼠24hUpro、NAG含量,改善肾功能,增强肾小管上皮细胞内MMP-9的表达,减轻顺铂引起的肾小管和肾小管间质损伤,对顺铂致大鼠肾损伤有一定的保护和治疗作用。

Objective To investigate the protective effect of Jia Wei HuangLian E-Jiao Tang on cisplatin （DDP）-induced nephrotoxicity in rats. Methods Male Sprague-Dawley rats were randomly divided into 5 groups （12 rats in each）： normal control, model group, sodium thiosulfate group, small- and large-dose Jia Wei HuangLian E-Jiao Tang group. Cisplatin （lg/L） was injected by 5 mg/KgBw through tail-vein at the same time each week for 3 weeks in a row for model group, sodium thiosulfate group, small- and large-dose Jia Wei HuangLian E-Jiao Tang group, but for group normal, the same amount of normal saline solution was injected. Intragastric administration was made once per day for 8 weeks continuously according to rat body-weight after the first injection. Normal saline （1 ml/100 gBw）was given to normal group and model group. The same volume of drugs dosage to other 3 groups was all 1 ml/100 gBw： When the test ended, kidney tissue of each group rats was wax-wrapped and treated with PAS colouring and immunohistochemistry staining to test the expression of MMP-9. Results For the contents of 24-hr urine protein and NAG, they were higher in model group than in normal controls （P〈0.01）, and lower in sodium thiosulfate group and two Chinese herb groups than in model group （P〈0.05 or 〈0.01） but no significant difference with normal controls （P〉0.05）. In normal group, no apparent pathological changes were found and the expression of MMP-9 was weak in renal tubular epithelial cell. Compared with normal, renal tubular epithelial cells in model group had a severe damage and interstitial fibroplasia, and its expression of MMP-9 was weak; While the lesions in treatment groups were slighter than that in group model, and the expression of MMP-9 was increased significantly. Conclusion For nephrotoxicity rats induced by cisplatin, Jia Wei HuangLian E-Jiao Tang may decrease the levels of 24-hr urine protein and NAG;The expression of MMP-9 may be up-regulation and therefore the nephrotoxicity induced by cisplatin may be relieved.