大蒜素对IgA肾病纤维化大鼠肾脏保护作用的研究

Protection function of tumor necrosis factor-a and a-smooth muscle actin in IgA nephropathy fibrosis

目的研究大蒜素对IgA肾病肾间质纤维化的影响,并探讨其可能的肾脏保护机制。方法联合IgA肾病模型及单侧输尿管结扎的方法建立IgA肾病纤维化的动物模型。将SD大鼠随机分为正常对照组、模型对照组及高、低剂量大蒜素治疗组,按各组相应药物剂量灌胃。于干预前、干预14天及28天检测各组大鼠尿红细胞计数、尿素氮水平及血清肿瘤坏死因子-α(TNF-α)、α-平滑肌肌动蛋白(α-SMA)含量;并于28天末光镜下观察各组大鼠肾脏的病理改变。结果与模型对照组相比,高、低剂量大蒜素治疗组大鼠尿红细胞计数(模型组-高剂量组,干预14天/28天,t=1.12/5.58;模型组-低剂量组,干预14天/28天,t=1.62/7.51)、尿素氮水平、血清TNF-α(模型组-高剂量组,干预14天/28天,t=3.48/11.95;模型组-低剂量组,干预14天/28天,t=4.76/12.78)、α-SMA含量(模型组-低剂量组,干预14天/28天,t=5.38/5.77)均降低(均P<0.05),肾小球系膜区IgA沉积强度明显减轻,肾组织病理纤维化程度亦有所减轻。大蒜素高、低剂量治疗组在降低尿红细胞计数(干预28天,t=1.99)、血清TNF-α(干预28天,t=3.73)和α-SMA(干预14天/28天,t=5.60/4.81)水平上差异均有统计学意义(均P<0.05),以大蒜素低剂量效果稍好。结论血清TNF-α和α-SMA在IgA肾病纤维化进展中进行性增高;大蒜素能够改善IgA肾病纤维化大鼠的临床症状、减轻肾脏病理学损害,可能通过降低血清TNF-α和α-SMA水平发挥抗肾脏纤维化的作用。

Objective To study the influence of diallyl trisulfide on IgA nephropathy renal interstitial fibrosis and to explore its possible renal protective mechanism. Methods IgA nephropathy fibrotic model in rats were established in study by combining IgA nephropathy model with unilateral ureteral obstruction. The healthy SD rats were randomly and equally divided into 4 groups： normal control group, model control group, high-dose dially trisulfide （ DATS） treatment group and low-dose DATS treatment group. The above groups were lavaged with corresponding drug. The urine and blood of rats were examined for urinary red blood cell count, blood urea nitrogen, TNF-αand α-SMA before intervention, 14 and 28 days after intervention. At the 28th day, all rats were sacrificed and their pathomorphological changes in kidneys were observed by immune fluorescence microscope. Results Compared with model control group, the levels of urine erythrocyte （model control group —high-dose DATS treatment group, at 14/28 days after intervention,t =1. 12/5. 58; model control group— low-dose DATS treatment group, at 14/28 days after intervention, t=1. 62/7. 51）, blood urea nitrogen, TNF-α （model control group—high-dose DATS treatment group, at 14/28 days after intervention, t =3. 48/11. 95; model control group —low-dose DATS treatment group, at 14/28 days after intervention,t=4. 76/12. 78） andα-SMA （model control group—low-dose DATS treatment group, at 14/28 days after intervention,t=5. 38/5. 77） reduced in both DATS treatment groups. The degree of IgA deposits at glomerular mesangial area and the renal pathological fibrosis relieved in both DATS treatment groups. There were significant differences between high-dose and low-dose DATS treatment groups in reducing the levels of urine erythrocyte （at 28 days after intervention,t=1. 99）, TNF-α （at 28 days after intervention,t=3. 73） and α-SMA （at 14/28 days after intervention,t=5. 60/4. 81） （all P〈0. 05）. The effect of low-dose DATS treatment was more obvious. Conclusion The levels of TNF-α and α-SMA increase progressively in IgA nephropathy fibrosis developing. The dially trisulfide can relieve the clinical symptoms and pathological damages in IgA nephropathy fibrotic rats, and can prevent the occurrence of renal interstitial fibrosis by reducing the levels of serum TNF-α and α-SMA.