目的观察六味地黄加味胶囊对糖尿病肾病(DN)大鼠肾脏的保护作用, 对肾脏蛋白激酶C(PKC)活性及结缔组织生长因子(CTGF)表达的影响。方法ip链脲佐菌素(STZ)建立大鼠DN模型, 模型成功后随机分为5组:对照组、模型组、洛汀新组、六味地黄加味胶囊组、洛汀新与六味地黄加味胶囊合用组, 药物干预12周后, 透射电镜观察各组大鼠肾脏超微结构, 免疫组织化学法检查肾皮质CTGF表达, 检测相对肾质量、血糖、尿白蛋白排泄率(UPER)、血肌酐(SCr)、尿肌酐(UCr)、内生肌酐清除率(CCr)、肾脏PKC活性等。结果DN大鼠肾脏胶原沉积明显, 相对肾质量、血糖、UPER、CCr、肾脏PKC活性、肾皮质CTGF表达等显著升高, 洛汀新、六味地黄加味胶囊及两药合用均可降低肾脏PKC活性和肾皮质CTGF的表达, 改善DN大鼠蛋白尿、肾功能, 减轻肾脏胶原沉积, 两药合用能更显著降低肾脏PKC活性、肾皮质CTGF的表达, 降低蛋白尿和改善肾功能作用更强。结论洛汀新、六味地黄加味胶囊及两药合用均能保护DN大鼠肾脏, 且两药合用较单用洛汀新作用更强。

Objective To investigate the protection of Liuwei Dihuang Jiawei Capsula(LDJ Capsula,Rehmanniae Capsula of Six Ingredients) on diabetic nephropathy(DN) rats' kidney and effect on renal protein kinase C(PKC) activity and connective tissue growth factor(CTGF) of DN rats.Methods The DN rat models were induced by ip injection of streptozotocin(STZ).The rats were randomly divided into five groups: control group; DN model group;Lotensin group;LDJ Capsula group;and Lotensis and LDJ Capsula combination group.Drug intervention term was 12 weeks.Renal ultrastructure was observed by transmission electron microscope and Masson staining.Relative kidney weight,blood glucose level,serum and urine creatinine content,creatinine clearance,excretion rate of the 24 hour urine protein,renal PKC activity,and CTGF expression in renal cortex were measured by immunohistochemistry.Results Deposition of collagen in renal of DN rats was conspicuous.Relative kidney weight,blood glucose level,serum and urine creatinine content,creatinine clearance,excretion rate of 24 h urine protein,renal PKC activity and CTGF expression of DN rats increased obviously.All Lotensin,LDJ Capsula,and the combination of these two drugs could decrease renal PKC activity and CTGF expression and ameliorate proteinuria and renal function of DN rats.At the same time they all could abate the deposition of collagen in renal of DN rats.Combination of these two drugs could decrease renal PKC activity and CTGF expression more ob-viously and at the same time had more notable protective effect on kidney of DN rats.Conclusion All Lotensin,LDJ Capsula,and the combination of these two drugs could protect kidney of DN rats.The combination of these two drugs has more obviously protective effect than using Lotensin only.

国家自然科学基金资助项目 (30600810)