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目的观察鳖甲煎丸对肾间质纤维化模型大鼠肾脏细胞增殖的影响,探讨其拮抗肾间质纤维化的作用机理。方法采用单侧输尿管结扎的方法复制大鼠肾梗阻模型,将其随机分为鳖甲煎丸组、缬沙坦组、模型组,并设假手术组。观察梗阻侧肾脏增殖细胞核抗原(PCNA)蛋白及基因的表达,同时检测肾间质细胞和肾小管细胞的增殖、凋亡以及细胞周期的变化。结果模型组及各治疗组大鼠肾脏中PCNA的蛋白及mRNA的表达和肾间质、肾小管细胞PCNA阳性细胞率、细胞凋亡率较假手术组明显升高(P<0.05,P<0.01),鳖甲煎丸组、缬沙坦组的表达均低于模型组(P<0.05,P<0.01),但是细胞凋亡与增殖的比值模型组较假手术组显著降低(P<0.05),2治疗组较模型组显著升高(P<0.05)。与假手术组相比,模型组处于S期的细胞比例显著增多(P<0.01),处于G0/G1期的细胞比例显著减少(P<0.01),与模型组比较,2治疗组S期的细胞比例明显降低(P<0.05),G0/G1期的细胞比例明显增加(P<0.01),G2/M期变化不明显。结论鳖甲煎丸能够下调肾间质纤维化大鼠肾间质细胞PCNA的蛋白及mRNA表达,促进肾间质细胞凋亡,抑制其增殖,阻止其由G0/G1期进入S期,对肾脏起到保护作用。
Objective To observe the effect of Biejiajianwan on renal cell proliferation in renal interstitial fibrosis model rats, and to explore the mechanism of its antagonistic effect on renal interstitial fibrosis. Methods Rat kidney obstruction models were made by unilateral ureteral ligation. They were randomly divided into Biejiajianwan group, Valsartan group and model group, and sham operation group was established. The expression of proliferating cell nuclear antigen (PCNA) protein and gene in the obstructed side of the kidney was observed, and the proliferation, apoptosis, and cell cycle changes of renal interstitial cells and renal tubular cells were measured. Results The expression of PCNA protein and mRNA in kidney and the rate of PCNA positive cells and apoptosis rate in renal interstitial and renal tubular cells were significantly higher in the model group and the treatment groups than in the sham operation group (P<0.05, P<0.01). The expressions of Biejiajianwan and valsartan were lower than those of the model group (P<0.05, P<0.01), but the ratio of apoptosis and proliferation in the model group was significantly lower than that in the sham operation group (P<0.05). , 2 treatment group was significantly higher than the model group (P <0.05). Compared with the sham group, the proportion of cells in the S phase of the model group increased significantly (P<0.01), and the proportion of cells in the G0/G1 phase decreased significantly (P<0.01). Compared with the model group, the S phase of the treatment group 2 The proportion of cells was significantly decreased (P<0.05), the proportion of cells in G0/G1 phase was significantly increased (P<0.01), and there was no significant change in G2/M phase. Conclusion Biejiajianwan can down-regulate the protein and mRNA expression of PCNA in renal interstitial cells of rats with renal interstitial fibrosis, promote apoptosis of renal interstitial cells, inhibit its proliferation, and prevent it from entering into S phase from G0/G1 phase to kidney. Play a protective role.