[Therapeutic mechanism of Shenbing Decoction Ⅲ for renal fibrosis in chronic kidney disease: a study with network pharmacology, molecular docking and validation in rats].
[Therapeutic mechanism of Shenbing Decoction Ⅲ for renal fibrosis in chronic kidney disease: a study with network pharmacology, molecular docking and validation in rats].
复制标题
DOI：
10.12122/j.issn.1673-4254.2023.06.07
复制
发表时间：
2023-06-20
影响因子：
--
通讯作者：
Sun, X
中科院分区：
文献类型：
--
作者：
Luo, G;Liu, H;Sun, X
目的：观察肾病汤Ⅲ号对5/6肾切除大鼠肾功能及病理的改善作用，并采用网络药理学结合分子对接分析其对慢性肾脏病肾纤维化的治疗机制。方法：40只雄性SD大鼠随机分为两组，分别接受二期5/6肾切除术（n=30）或假手术（n=10），末次手术后2周，检测血清测量大鼠的肌酐水平。肾切除大鼠随机分为肾病汤Ⅲ组、氯沙坦组和模型组，自5/6肾切除术后1周开始每日灌胃相应药物。治疗16周后，测定大鼠血清肌酐、尿素氮水平，并采用HE染色和Western blotting检测肾脏病理及纤维化相关因素的变化。采用网络药理学结合分子对接研究探讨肾病汤Ⅲ抗慢性肾脏病肾纤维化的治疗机制，并采用Western blotting验证核心靶点的表达。结果：与模型组相比，5/6肾切除加肾病汤Ⅲ治疗组大鼠血清肌酐、尿素氮水平显着降低，肾脏病理减轻，上皮间质转化相关蛋白变化改善。网络药理学分析显示，肾病Ⅲ号汤主要活性成分为金合欢素、芹菜素、尤帕提林、槲皮素、山奈酚、木犀草素，关键靶点包括STAT3、SRC、CTNNB1、PIK3R1、AKT1。分子对接研究表明，肾病Ⅲ号汤活性成分与关键靶点具有良好的结合活性。 Western blotting结果显示，肾病Ⅲ号汤治疗5/6肾切除大鼠肾组织中STAT3、PI3K、AKT蛋白表达明显恢复。结论：肾病Ⅲ号汤可减轻5/6肾切除大鼠肾损伤，其治疗作用可能是由其主要药理活性成分通过调节STAT3、PIK3R1、 AKT1。
OBJECTIVE: To observe the effect of Shenbing Decoction Ⅲ for improving renal function and pathology in rats with 5/6 nephrectomy and analyze its therapeutic mechanism for renal fibrosis in chronic kidney disease using network pharmacology combined with molecular docking.METHODS: Forty male SD rats were randomized into two groups to receive two-staged 5/6 nephrectomy (n=30) or sham operation (n=10), and 2 weeks after the final operation, serum creatinine level of the rats was measured. The rats with nephrectomy were further randomized into Shenbing Decoction Ⅲ group, losartan group and model group for daily treatment with the corresponding drugs via gavage starting at 1 week after 5/6 nephrectomy. After 16 weeks of treatment, serum creatinine and urea nitrogen levels of the rats were measured, and HE staining and Western blotting were used to examine the changes in renal pathology and fibrosis-related factors. Network pharmacology combined with molecular docking study was performed to explore the therapeutic mechanism Shenbing Decoction Ⅲ against renal fibrosis in chronic kidney disease, and Western blotting was used to verify the expressions of the core targets.RESULTS: Compared with those in the model group, the rats receiving 5/6 nephrectomy and Shenbing Decoction Ⅲ treatment showed significantly reduced serum creatinine and urea nitrogen levels, lessened renal pathologies, and improvement of the changes in epithelial mesenchymal transition-related proteins. Network pharmacological analysis showed that the main active ingredients of Shenbing Decoction Ⅲ were acacetin, apigenin, eupatilin, quercetin, kaempferol and luteolin, and the key targets included STAT3, SRC, CTNNB1, PIK3R1 and AKT1. Molecular docking study revealed that the active ingredients of Shenbing Decoction Ⅲ had good binding activity to the key targets. Western blotting showed that in rats with 5/6 nephrectomy, treatment with Shenbing Decoction Ⅲ obviously restored the protein expression of STAT3, PI3K, and AKT in renal tissue.CONCLUSION: Shenbing Decoction Ⅲ can reduce renal injury induced by 5/6 nephrectomy in rats, and its therapeutic effects are mediated possibly by its main pharmacologically active ingredients that alleviate renal fibrosis via modulating multiple targets including STAT3, PIK3R1, and AKT1.