BrdU标记法探讨糖尿病大鼠H_2S与细胞外基质积聚的关系

Investigation on the Relationship of H_2S and the Accumulation of Extracellular Matrix of the Diabetic Nephropathic Rats By Brd U labeling method

目的探讨硫化氢(hydrogen sulfide,H2S)与糖尿病肾病(diabetic nephropathy,DN)大鼠肾细胞外基质过度积聚的关系。方法 21只SD大鼠随机分成正常对照组(对照组)、糖尿病肾病组(DN组)、硫化氢干预组(DN+H2S组)。链脲佐菌素(STZ)法建立糖尿病大鼠模型,DN+H_2S组给予Na HS治疗8周,其他组给予同等剂量的0.9%生理盐水治疗。观察3组大鼠肾脏病理改变、Brd U阳性细胞和α平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)分布差异。结果与对照组比较,DN组大鼠尿蛋白量、相对肾重均明显增多,病理呈典型的DN改变,Brd U阳性细胞比值、肾小球α-SMA表达和分布显著增多(P<0.01);应用NaHS治疗后,大鼠肾脏DN改变明显减轻(P<0.01),BrdU阳性细胞比值、肾小球α-SMA表达和分布与正常对照组比较,差异无统计学意义(P>0.05)。结论 H_2S可以抑制DN大鼠肌性成纤维细胞增殖,减少α-SMA表达和分布,减缓DN大鼠的肾小球细胞外基质积聚。

Objective To explore the relationship of hydrogen sulfide （H2S） and the extracellular matrix of the diabetic nephropathic rats＇ glomerulars. Methods Twenty-one male rats（Sprague-Dawley） were randomly divided into Control group（n=7）, DN group（n=7） and DN＋H2S group （n=7）. Diabetes was induced in the rats except Control group rats by STZ（60mg/kg）. The rats of the DN＋H2S group were injected with NaHS every day,and rats of other groups were injected with NS. Eight weeks later, three groups were compared in proteinuria of 24 hours, KW/BW, the proportion of the BrdU positive cell and the distribution of α-SMA in glomerulars. Results Compared with Control group, DN group rats were significantly increased in proteinuria of 24 hours and KW/BW（P〈0.01）. Kidney biopsy in DN groups rats were typical DN pathological manifestation. In treatment with NaHS, the DN rats in the DN＋H2S group were decreased in proteinuria of 24 hours, KW/BW, the proportion of the BrdU positive cell and the distribution of α-SMA in glomerulars（P〈0.01）,and was similar with the control group in the pathology of renal. Conclusion The H2S control the multiplication of myofibroblast, and were decreased in the distribution of α-SMA in glomerulars. The H2S treatment may put off the progress of the extracellular matrix in the DN rats＇ glomerulars.