WANG You, ZHANG Chengfei, ZHOU Luoqing, JIA Xiaolei, QIN Lingling, WANG Haiyan, WU Lijia, HUANG Yukun, BAO Xincui, YANG Jing, LYU Cuiyan, LIU Tonghua
China Journal of Traditional Chinese Medicine and Pharmacy. 2024, 39(11): 5849-5855.
Objective: To observe the protective effect and mechanism of Bushen Kaixuan Tongluo Formula (BKTF) on the kidney of db/db mice. Methods: Thirty db/db mice were randomly divided into five groups based on fasting blood glucose levels: the model group, the irbesartan group, the low-dose, the medium-dose and the high-dose BKTF groups, six in each group, and six m/m mice were included as the normal group. Every 2 weeks, the body weight of mice in each group was measured. After 12 weeks of continuous administration, specimens were collected for measurement of fasting blood glucose, urinary albumin, urinary creatinine, urinary albumin creatinine ratio (ACR), serum creatinine (Scr), urea, serum total cholesterol (TC), triglycerides, insulin (INS), aspartate aminotransferase, and alanine aminotransferase levels. Kidney sections were embedded and subjected to staining with Hematoxylin-Eosin (HE), Periodic Acid-Schiff (PAS), and Masson's trichrome. Immunohistochemical and RT-qPCR detected PPARγand ERK1/2 protein and mRNA expression in the kidney. Results: Compared with the model group, the body weight of mice in the each dose BKTF group was significantly reduced (P<0.05), the urine ACR level of mice in the medium-and high-dose BKTF groups was reduced (P<0.01, P<0.05), the Scr and TC level of mice in the medium-dose BKTF group was reduced (P<0.05, P<0.01), the INS content of all dose BKTF groups was reduced (P<0.01). All doses BKTF groups could can alleviate the dilation of capillaries in the glomerulus, thickening of the basement membrane, and degeneration and necrosis of renal tubular epithelial cells, reduce glycogen deposition, and improve the level of renal fibrosis. Immunohistochemical detection showed that compared with the model group, the group of all dose BKTF groups had the levels of PPARγ protein signifcantly increased (P<0.01), while the levels of ERK1/2 protein decreased (P<0.01). RT-qPCR detection showed that compared with the model group, the group of medium- and high-dose BKTF groups had the levels of PPARγ mRNA signifcantly increased (P<0.01), while the levels of ERK1 mRNA decreased (P<0.01), and the group of all dose BKTF groups had the levels of ERK2 mRNA signifcantly decreased (P<0.01). Conclusion: BKTF can improve the renal function of diabetes nephropathy mice, reduce urinary protein, and alleviate kidney damage. Its mechanism may be related to PPARγ/ERK1/2 signaling pathway.
