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

Regulating effects of Cordyceps sinensis capsule and telmisartan tablets on renal tubular epithelial-mesenchymal transitionin in diabetic nephropathy rats

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 regulating effects of telmisartan and Cordyceps sinensis on renal tubular epithelial -mesenchymal transitionin in diabetic ncphropathy rats. Methods The diabetic nephropathy rat model was established by single intraperitoneal injection of streptozotocin. Fifty diabetic nephropathy rats were randomly divided in to normal group, model group, telmisartan group （8 mg · kg^-1）, Cordyceps sinensis group （2. 5 g · kg^-1 ） , combination group （8 mg · kg^-l telmisartan ＋ 2. 5 g · kg^-1 Cordyceps sinensis）. Rats in the five groups were all trea- ted for 8 weeks. After 8 weeks of treatment, the serum creatinine （SCr）, blood urea nitrogen （BUN） and 24 h urinary protein were tested.The urine was selected and content of 24 hours urinary protein were tested. The changes of renal tubular interstitial was examined by HE and masson staining for kidney tissue. The expression of alpha smooth muscle actin （SMA）, bone morphogenetic protein 7 （ BMP - 7 ） and transforming growth factor beta （ TGF -β） protein was tested by immunohisto- chemical assay. Results α -SMA expression were 1.09±0.93 and 20. 19 ±3. 11 in normal and model groups with statistical difference（P 〈0. 051） ;α - SMA expression werel7.02 ± 1.13,16. 68 ±2. 77 and 11.76±4. 41 in Cordyceps sinensis, telmisartan and combined groups respectively which was significant lower than model group （P 〈 0. 05 ）. TGF-β expression was 2. 40 ± 1.07 and 6. 31 ± 1.68 in normal and model groups with statistical difference （P 〈0. 05） ; TGF - 13 expression were 4. 78± 0. 61,4. 60 ± 1.14 and 4. 21 ＋0. 36 in Cordyceps sinensis, telmisartan and combined groups respectively which was significant lower than model group （ P 〈 0. 05 ）. The BMP - 7 expression were 9. 85 ± 1.89 and 2. 76 ± 1.29 in normal and model groups, which indicated model group was significant lower than normal group（P 〈0. 05 ） ; BMP - 7 expression were 6. 08 ± 1.03,5.84 ± 1.17 and 5.26± 1.28 in Cordyceps sinensis, telmisartan and combined groups respectively which was significant higher than model group （P 〈 0. 05）. Conclusion The epithelial -mesenchymal transition procedure in diabetic nephropathy rats can be inhibit by Cordyceps sinensis combined with telmisartan through induced expression of BMP - 7 and inhibition expression of TGF-β and α- SMA.