Li Jiarui, Zhuang Yuan, Fan Guoyong, Wang Simeng, Yan Enhui, Guo Jianpeng, Zhang Chi, Jiang Shicui
Wenzhou Key Laboratory for the Diagnosis and Prevention of Diabetic Complications, The Third Affiliated Hospital of Wenzhou Medical University (Ruian People's Hospital), Ruian, China.
College of Pharmacy, Yanbian University, Yanji, Jilin, China.
Front Pharmacol. 2024 Dec 6;15:1480626. doi: 10.3389/fphar.2024.1480626. eCollection 2024.
Fibrosis is key in the development and progression of diabetic kidney disease (DKD). Baicalin (BA), wogonin (WGN), and wogonoside (WGS) have renoprotective effects. The mechanism of alleviation of DKD progression, by improving renal fibrosis, is unclear. This study aimed to investigate the mechanisms and effects of a Georgi. (Lamiaceae) mixture (MIX, WGN:BA:WGS = 4:2:1) on DKD in a spontaneous DKD model.
Male mice were controls, and mice were diabetes models. Both groups received daily oral gavage of normal saline. Treatment groups received daily oral gavage of BA or MIX (20 mg/kg) for 10 weeks. Biochemical indicators and kidney lesions were assessed. Fibrosis-related proteins were detected by immunoblotting, immunohistochemistry, and real-time fluorescence quantitative PCR.
MIX significantly reduced body weight (40.97 ± 1.43 vs. 42.26 ± 1.60), improved insulin sensitivity (63.70 ± 8.98 vs. 109.48 ± 0.69), lowered the renal hypertrophy index (19.81 ± 2.86 vs. 28.94 ± 0.256), and decreased blood urea nitrogen levels (7.57 ± 0.79 vs. 9.57 ± 0.38) and the urine protein/creatinine ratio (0.50 ± 0.06 vs. 0.80 ± 0.18). MIX also enhanced lipid profiles and renal function by improving renal tubular dilation, restoring renal structures, and reducing glomerulosclerosis, basal membrane thickening, and glycogen deposition. These effects were achieved by reducing the protein and gene expression of collagen II (Col-II), connective tissue growth factor, and collagen I (Col-I).
MIX inhibits the transforming growth factor-β/Smads signaling pathway, thus alleviating renal fibrosis, and can be used to develop a treatment for DKD.
纤维化是糖尿病肾病（DKD）发生和发展的关键因素。黄芩苷（BA）、汉黄芩素（WGN）和黄芩苷（WGS）具有肾脏保护作用。通过改善肾纤维化来减轻DKD进展的机制尚不清楚。本研究旨在探讨唇形科植物糙苏属混合物（MIX，WGN:BA:WGS = 4:2:1）对自发性DKD模型中DKD的作用机制和效果。
雄性小鼠作为对照组，另一组作为糖尿病模型组。两组均每日口服生理盐水。治疗组每日口服BA或MIX（20 mg/kg），持续10周。评估生化指标和肾脏病变。通过免疫印迹、免疫组织化学和实时荧光定量PCR检测纤维化相关蛋白。
MIX显著降低体重（40.97±1.43 vs. 42.26±1.60），改善胰岛素敏感性（63.70±8.98 vs. 109.48±0.69），降低肾脏肥大指数（19.81±2.86 vs. 28.94±0.256），降低血尿素氮水平（7.57±0.79 vs. 9.57±0.38）和尿蛋白/肌酐比值（0.50±0.06 vs. 0.80±0.18）。MIX还通过改善肾小管扩张、恢复肾脏结构以及减少肾小球硬化、基底膜增厚和糖原沉积来增强脂质谱和肾功能。这些作用是通过降低Ⅱ型胶原（Col-II）、结缔组织生长因子和Ⅰ型胶原（Col-I）的蛋白和基因表达来实现的。
MIX抑制转化生长因子-β/Smads信号通路，从而减轻肾纤维化，可用于开发DKD的治疗方法。
