Xiaoke Decoction Inhibits COX-2-Mediated LDLr Pathway Dysfunction and Protects Renal Function in Diabetic Nephropathy Rats.

IF 1.5 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Zhi-Qi Tang, Yuan-Xia Liu, Ling-Jia Tao, Jin-Ye Song, Tong-Rui Weng, Teng Fan
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引用次数: 0

Abstract

Objective: Traditional Chinese medicine exhibits positive therapeutic effects as a primary or adjunctive treatment for diabetic nephropathy (DN). This study aimed to evaluate the impact and mechanism of action of Xiaoke decoction (XKD), a traditional Chinese medicine, on renal function in DN rats.

Methods: A rat model of DN was established, and the rats were divided into five groups (n = 7 per group): normal control group (NC), DN model group (DN), low-dose XKD treatment group (DN + XKD-L, 1.5 g/kg/d), high-dose XKD treatment group (DN + XKD-H, 6 g/kg/d), and cyclooxygenase-2 (COX-2) inhibitor (NS398) treatment group (DN + NS398, 8 mg/kg/d). Medications were administered via gavage for 12 consecutive weeks, while equal volumes of normal saline were given to the NC and DN groups. A glucometer was used to detect changes in blood glucose (BG). Enzyme-linked immunosorbent assay (ELISA) and an automatic biochemical analyzer were employed to measure levels of insulin, serum creatinine (Scr), blood urea nitrogen (BUN), triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and 24-h urine protein quantity (UP/24 h) in rats. Renal tissue sections from different treatment groups were prepared, with tissue lesions examined via periodic acid-Schiff (PAS) and hematoxylin-eosin (HE) staining. Tissue inflammation and lipid deposition were evaluated using ELISA and Oil Red O staining. Immunohistochemistry and Western blotting were used to detect changes in the expression levels of COX-2 and low-density lipoprotein receptor (LDLr) in tissues, and to clarify the regulatory mechanism of XKD on renal function in DN rats.

Results: XKD, particularly at the high dose (XKD-H, 6 g/kg/d), significantly reduced BG, insulin levels, renal weight ratio, Scr, BUN, and UP/24 h in DN rats. DN rats showed significant renal lesions, and XKD gavage (especially XKD-H) markedly improved these pathological changes. In DN rats, XKD significantly decreased the protein expression levels of COX-2 and LDLr, downregulated the levels of inflammatory factors and lipid factors, reduced lipid deposition in renal tissues, and ameliorated structural abnormalities in glomeruli, basement membranes, and renal tubules.

Conclusions: XKD alleviates renal tissue damage by regulating the COX-2-mediated LDLr pathway, thereby reducing the release of inflammatory factors and lipid accumulation in DN rats and protecting renal function.

消渴汤抑制cox -2介导的LDLr通路功能障碍,保护糖尿病肾病大鼠肾功能。
目的:中药作为糖尿病肾病(DN)的主要或辅助治疗方法具有良好的疗效。本研究旨在探讨中药消咳汤对DN大鼠肾功能的影响及其作用机制。方法:建立DN大鼠模型,将大鼠分为5组(每组7只):正常对照组(NC)、DN模型组(DN)、低剂量XKD治疗组(DN + XKD- l, 1.5 g/kg/d)、高剂量XKD治疗组(DN + XKD- h, 6 g/kg/d)、环氧化酶-2 (COX-2)抑制剂(NS398)治疗组(DN + NS398, 8 mg/kg/d)。NC组和DN组分别给予等量生理盐水灌胃,连续灌胃12周。血糖仪用于检测血糖(BG)的变化。采用酶联免疫吸附法(ELISA)和全自动生化分析仪检测大鼠胰岛素、血清肌酐(Scr)、尿素氮(BUN)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)和24 h尿蛋白量(UP/24 h)。制备不同治疗组肾组织切片,采用周期性酸-希夫(PAS)和苏木精-伊红(HE)染色检查组织病变。采用ELISA法和油红O染色评价组织炎症和脂质沉积。采用免疫组织化学和Western blotting检测DN大鼠组织中COX-2和低密度脂蛋白受体(low-density lipoprotein receptor, LDLr)表达水平的变化,阐明XKD对DN大鼠肾功能的调节机制。结果:XKD,特别是在高剂量(XKD- h, 6 g/kg/d)下,显著降低DN大鼠BG、胰岛素水平、肾重比、Scr、BUN和UP/24 h。DN大鼠表现出明显的肾脏病变,XKD灌胃(尤其是XKD- h)明显改善了这些病理改变。在DN大鼠中,XKD显著降低COX-2和LDLr蛋白表达水平,下调炎症因子和脂质因子水平,减少肾组织脂质沉积,改善肾小球、基底膜和肾小管结构异常。结论:XKD通过调节cox -2介导的LDLr通路,减轻DN大鼠肾组织损伤,从而减少炎症因子的释放和脂质积累,保护肾功能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current Medical Science
Current Medical Science Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
4.70
自引率
0.00%
发文量
126
期刊介绍: Current Medical Science provides a forum for peer-reviewed papers in the medical sciences, to promote academic exchange between Chinese researchers and doctors and their foreign counterparts. The journal covers the subjects of biomedicine such as physiology, biochemistry, molecular biology, pharmacology, pathology and pathophysiology, etc., and clinical research, such as surgery, internal medicine, obstetrics and gynecology, pediatrics and otorhinolaryngology etc. The articles appearing in Current Medical Science are mainly in English, with a very small number of its papers in German, to pay tribute to its German founder. This journal is the only medical periodical in Western languages sponsored by an educational institution located in the central part of China.
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