延肾胶囊延缓残肾损伤的实验研究

An experimental study on Yan-Shen capsule retarding remnant kidney damage

目的 探讨延肾胶囊延缓残肾进行性损伤的量效关系。方法 Wistar大鼠 12 0只 ,随机分为 6组 ,A组为假手术对照组 ;B组为 5 / 6肾切除 ;C、D、E组分别为 5 / 6肾切除 +低、中、高剂量延肾胶囊 ;F组为 5 / 6肾切除 +肾衰宁。于术后 15天、90天测定血尿素氮 (BUN)、血肌酐 (SCr)、血红素 (Hb) ,肾组织光镜及其形态计量、电镜。结果 C、D、E组BUN和 SCr低于 B组 ,随着延肾胶囊剂量增加 ,BUN和 SCr逐渐降低 ;术后光镜下硬化肾小球比率和病变肾小管肾间质比率逐渐降低 ;F组硬化肾小球比率和病变肾小管肾间质比率低于 B组 ,但高于 D、F两组。电镜观察 ,可见增生的系膜细胞凋亡 ,A组无明显异常发现。结论 延肾胶囊能显著降低血 BUN、SCr,抑制残肾纤维化 ,延缓慢性肾衰的进展 ,呈剂量依赖性 ,其效果优于肾衰宁 ;延肾胶囊促进增生的系膜细胞凋亡可能是其抑制残肾纤维化、保护残肾功能的重要机制之一。

Objective To clarify the dosage effect relation of Yan Shen Capsule to retard remnant kidney progressive damage. Methods 120 adult Wistar rats were randomly divided into 6 groups, 20 rats in each group. Rats in Group A were sham operated, and rats in Groups B, C, D, E and F were 5/6 nephrectomized. After operation, Groups C, D, E were given low (450 mg/kg/d), middle (900 mg/kg/d) and high (1800 mg/kg/d) dosage of Yan Shen capsule into the stomach. Group F was given control drug, Shen Shuai Ning Capsule. Groups A and B were given the same volume of saline. On day 15 and 90 after operation, serum urea (BUN) and creatinine (SCr), hemoglobin (Hb), renal histology under optical microscope and transelectron microscope, and morphometry were observed. Results Ninety days after operation, the concentration of BUN and SCr in Group B was obviously higher and Hb was lower than that in Group A ( P <0.05). The concentration of BUN and SCr in Groups C, D, and E was lower and Hb was higher than that in Group B( P <0.05). The higher the dosage of Yan Shen capsule was, the lower the concentration of BUN and SCr. The concentration of BUN and SCr in Group F was lower than that in Group B but higher than that in Group E. Under optical microscope, the remnant kidney in Group B showed glomerular mesangial cell proliferation, glomerular mesangial matrix dilation, glomerular sclerosis and interstitial fibrosis. The longer the time was after operation, the more serious the renal histological damage. The morphometry showed that Group B had higher ratio of sclerosis glomeruli and damaged tubules and interstitial than did Group A ( P <0.05). Groups C, D, and E had lower ratio of sclerosis glomeruli and damaged tubules and interstitial than did Group B ( P <0.05). The higher the dosage of Yan Shen capsule was, the lower the ratio of sclerosis glomeruli and damaged tubules and interstitial. Under transelectron microscope, the glomerular mesangial cell proliferation was outstanding in Group B with less apoptosis cells in mesangium. In Groups C, D, and E, glomerular mesangial cell apoptosis was obvious with less proliferative mesangial cells. In Group A, there were neither obvious apotosis nor proliferation in mesangium.Conclusion Yan Shen Capsule could reduce BUN and SCr, inhibit the fibrosis of remnant kidney, and retard the progress of chronic renal failure in dosage dependent manner. Yan Shen capsule has better protective effects on theremnant kidney than Shen Shuai Ning capsule does. Promoting apoptosis of proliferative mesangial cells might be one of the mechanisms that Yan Shen capsule inhibit fibrosis and protects function of remnant kidney.