冬虫夏草胶囊联合替米沙坦片对糖尿病肾病大鼠肾小管上皮细胞转分化的调节作用

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目的研究冬虫夏草联合替米沙坦对糖尿病肾病大鼠肾小管上皮细胞转分化的调节作用。方法用链脲佐菌素腹腔内注射建立糖尿病肾病大鼠模型,50只大鼠按照体重随机分为正常组、模型组、替米沙坦组(8 mg·kg~(-1))、冬虫夏草组(2.5 g·kg~(-1))及联合组(替米沙坦8 mg·kg~(-1)+冬虫夏草2.5 g·kg~(-1)),均给药8周。于造模8周后,以常规方法检测血清肌酸酐(SCr)、尿素氮(BUN)。收集24 h尿液,检测24 h尿蛋白含量。取肾组织,用HE、Masson染色观察肾小管间质病变,以免疫组织化学染色法观察α平滑肌肌动蛋白(α-SMA)、骨形态发生蛋白-7(BMP-7)和转化生长因子-β(TGF-β)肾间质的阳性染色表达,并进行半含量分析。结果与正常组的α-SMA表达为1.09±0.93比较,模型组的α-SMA的表达为20.19±3.11,明显升高,差异有统计学意义(P<0.01);冬虫夏草组、替米沙坦组及联合用药组的α-SMA的表达分别为17.02±1.13,16.68±2.77,11.76±4.41,与模型组比较均明显减少,差异有统计学意义(P<0.01)。与正常组的TGF-β表达为2.40±1.07比较,模型组TGF-β的表达为6.31±1.68,明显升高,差异有统计学意义(P<0.01);冬虫夏草组替、米沙坦组及联合用药组的TGF-β表达分别为4.78±0.61,4.60±1.14,4.21±0.36,与模型组比较均明显减少,差异有统计学意义(P<0.01)。与正常组的BMP-7表达为9.85±1.89比较,模型组的BMP-7表达为2.76±1.29,明显减少,差异有统计学意义(P<0.01);冬虫夏草组替、米沙坦组及联合用药组的BMP-7表达分别为6.08±1.03,5.84±1.17,5.26±1.28,与模型组比较均明显增加,差异有统计学意义(P<0.01)。结论替米沙坦联合冬虫夏草可能通过诱导BMP-7的高表达、抑制TGF-β与α-SMA的表达,从而抑制肾小管上皮细胞间充质转分化的发生发展。 Objective To study the regulatory effect of Cordyceps sinensis plus telmisartan on renal tubular epithelial cell transdifferentiation in diabetic nephropathy rats. Methods The model of diabetic nephropathy was established by intraperitoneal injection of streptozotocin. Fifty rats were randomly divided into normal group, model group, telmisartan group (8 mg · kg -1), Cordyceps sinensis (2.5 g · kg -1) and combination group (8 mg · kg -1 of telmisartan and 2.5 g · kg -1 of Cordyceps sinensis) were administered for 8 weeks. After 8 weeks of modeling, serum creatinine (SCr) and blood urea nitrogen (BUN) were detected by routine methods. Urine collected 24 h, 24 h urinary protein content. The renal tissue was harvested and the tubulointerstitial lesions were observed by HE and Masson staining. The expressions of α-SMA, BMP-7 and TGF-β were detected by immunohistochemical staining. β (TGF-β) renal interstitium staining and semi-content analysis. Results Compared with normal group, the expression of α-SMA was 1.09 ± 0.93, the expression of α-SMA in model group was 20.19 ± 3.11, which was significantly higher than that in normal group (P <0.01) The expression of α-SMA in the combination group and the combination group was 17.02 ± 1.13, 16.68 ± 2.77 and 11.76 ± 4.41, respectively, which were significantly decreased compared with the model group (P <0.01). Compared with normal group, the expression of TGF-β was 2.40 ± 1.07, the expression of TGF-β in model group was 6.31 ± 1.68, which was significantly higher than that in normal group (P <0.01) Compared with the model group, the expression of TGF-β in the combination group was 4.78 ± 0.61, 4.60 ± 1.14 and 4.21 ± 0.36, respectively, and the difference was statistically significant (P <0.01). Compared with normal group, the expression of BMP-7 was 9.85 ± 1.89, the expression of BMP-7 in model group was 2.76 ± 1.29, which was significantly lower than that in normal group (P <0.01) The expression of BMP-7 in the treatment group was 6.08 ± 1.03, 5.84 ± 1.17 and 5.26 ± 1.28, respectively, which were significantly increased compared with the model group (P <0.01). Conclusion Telmisartan combined with Cordyceps sinensis may inhibit the occurrence and development of renal tubular epithelial mesenchymal transdifferentiation by inducing the high expression of BMP-7 and inhibiting the expression of TGF-β and α-SMA.
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