昆仙胶囊对IgA肾病大鼠的肾保护作用及系膜细胞增殖的影响

Renal protection effect of kunxian capsule on rat with IgA nephropathy and its influence on mesangial cell proliferation

目的本实验通过建立IgA肾病大鼠模型及大鼠肾小球系膜细胞体外实验,进行药物干预,探讨昆仙胶囊的肾保护作用和对系膜细胞增殖的影响。方法 48只雌性SD大鼠随机均分为正常组、IgAN模型组、缬沙坦组、昆仙胶囊组,每组12只,造模第5周开始灌胃给药,分别于第10周、16周每组每次随机挑选6只大鼠,检测24 h尿蛋白定量、血肌酐、尿素氮,观察大鼠肾脏IgA免疫荧光和病理学改变。同时,选择IgA1刺激大鼠系膜细胞,将系膜细胞分为正常组、模型组、缬沙坦高低剂量组和昆仙胶囊高中低剂量组,CCK8检测药物干预后细胞增殖及抑制情况。结果第10周、16周昆仙胶囊组IgAN大鼠24 h尿蛋白定量、肾功能指标较模型组有显著性差异(P<0.05),与缬沙坦组比较无明显统计学差异(P>0.05)。同时肾组织病理均提示昆仙胶囊组病变程度较模型组轻。细胞实验提示经IgA1刺激后可引起系膜细胞增殖,药物干预后昆仙胶囊能够明显抑制IgA1诱导的大鼠系膜细胞增殖。结论本实验说明昆仙胶囊能减少IgAN大鼠尿蛋白,延缓肾功能进展,减缓肾组织病理改变,其机制可能是通过抑制系膜细胞增殖而达到的。

Objective To investigate the renal protection effect of kunxian capsule on rats with IgA nephropathy and its influence on mesangial cell proliferation through establishing a rat model of IgA nephropathy and rat mesangial cells in vitro experiment for drug intervention. Methods Forty-eight female SD rats were randomLy divided into the normal group, IgAN model group, valsartan group and kunxian capsule group, with 12 rats in each group. The drugs were intragastrically administered from week 5 of modeling. Six rats were selected from each group and each time in week 10 and week 16 to detect the 24 hour urine protein quantitation, serum creatinine and urea nitrogen and observe the IgA immunofluorescence and pathological changes of rat kidney. Meanwhile, IgA1 was selected to stimulate rat mesangial cells, and the mesangial cells were divided into the normal group, model group, valsartan high-low dose group and Kunxian capsule high-medium-low dose group. CCK8 was used to detect the cell proliferation and inhibition after drug intervention. Results In week 10 and week 16, there were significant differences in the 24 hour urine protein quantitation and renal function indicators between the kunxian capsule group and the model group(P<0.05), but there was no statistically significant difference between the kunxxia capsule group and the valsartan group(P>0.05). At the same time, it was suggested by renal tissue pathology that the degree of lesions in the kunxian capsule group was lower than that in the model group. It was suggested by cellular experiment that mesangial cell proliferation could be induced by IgA1 stimulation and kunxian capsule could significantly inhibit IgA1-induced proliferation of rat mesangial cells. Conclusion This experiment demonstrates that kunxian capsule can reduce the urine protein of IgAN rats, delay the progression of renal function and slow down the pathological changes of renal tissues. The mechanism may be achieved by inhibiting the proliferation of mesangial cells.