慢性肾衰大鼠肾小球细胞增殖凋亡的研究

Glomerular cell proliferation and apoptosis in experimental glomerulosclerosis

目的:探讨肾小球细胞凋亡在肾小球硬化进程中的可能作用。方法:建立阿霉素肾硬化大鼠模型,检测其肾小球有核细胞计数。用RT-PCR方法和免疫组化法检测增殖细胞核抗原的表达,原位检测肾小球细胞凋亡指数。结果:疾病组各时间点增殖指数和凋亡指数明显升高(P<0.01),且均于12周达高峰,但疾病组4周和8周前者明显高于后者,而12周时,后者则明显高于前者。疾病组肾小球中凋亡指数与增殖指数呈密切正相关(P<0.05),有核细胞与肾小球细胞凋亡指数之间存在明显负相关,相关系数为0.7456。结论:实验性肾小球硬化大鼠中肾小球细胞凋亡是清除过度增殖细胞的一种机制,但过度的细胞凋亡又可能导致肾小球内固有细胞减少,加重肾小球硬化进展。

Objective To evaluate the effects of glomen.dar cell proliferation and apoptosis in experimental glomeruloselerosis. Methods The uninephrectomy with twice intravenous adriamycin injection model of chronic glomeruloselerosis was studied in adult male Wistar rats. The renal function, glomerular cell proliferation and apoptosis were examined at 4, 8, 12 weeks after the first intravenous adriamycin injection. Mean arterial pressure and average glomerolar area（Ac） and volume（Vc） were detected at the end of the study. Apoptosis was assessed by in situ dutp biotin nick-end labeling method （TUNEL） . Proliferation was determined by immunohistochemistry and RT-PCR of proliferation cell nuclear antigen（PCNA） . Results The number of apoptotic glomerular cells gradually increased and reached to the peak at 12 weeks. 4, 8 and 12 versus 0. 00 ± 0.00 in control respectively, P 〈 0. 01. Parallel changes in the number of PCNA positive glomerular cells wereobserved（proliferative cells 3.15 ± 0. 55, 4. 42 ± 0. 60, 8.08 ± 0. 70 versus 0. 00 ± 0. 00 in control, P 〈 0.01 ）, although the increase in apoptosis was greater than that in proliferation. Conclusion It is suggested that more excess apoptosis over proliferation is involved in the genesis and progression of glomerulosclerosis.