Zhang Zhong-Yong, Wang Yu-Ming, Wang Ning, Wang Yuan-Song, Zhang Hui, Wang Duo, Wang Li-Xin, Cui Huan-Tian, Wen Wei-Bo, Lv Shu-Quan, Cao Yong-Jun
Department of Endocrinology, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou 061012, Hebei Province, China.
College of Integrative Chinese and Western Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
World J Diabetes. 2025 May 15;16(5):103511. doi: 10.4239/wjd.v16.i5.103511.
Diabetic nephropathy (DN) is a major complication of diabetes, marked by progressive renal damage and an inflammatory response. Although research has investigated the pathological mechanisms underlying DN, effective treatment options remain limited.
To evaluate the therapeutic impact of Shenzhuo formulation (SZF) on a DN mouse model and to examine its potential molecular mechanisms using transcriptomic and metabolomic approaches.
We established a DN mouse model through a high-fat diet combined with streptozotocin (STZ) injection, followed by SZF treatment. We analyzed SZF's effects on gene expression and metabolite profiles in renal tissues of DN mice using transcriptomics and metabolomics techniques. Additionally, based on transcriptomic and non-targeted metabolomic findings, we further assessed SZF's influence on the expression of factors related to the cytochrome P450 (CYP450)-mediated arachidonic acid (AA) metabolism pathway, as well as its effects on inflammation and oxidative stress.
SZF intervention significantly decreased hyperglycemia and mitigated renal function impairment in DN mice. Pathological analysis revealed that SZF treatment improved renal tissue damage, reduced fibrosis, and diminished glycogen deposition. Transcriptomic analysis indicated that SZF influenced mRNA expression of CYP450-related genes, including , , /, , , and . Non-targeted metabolomic results demonstrated that SZF altered the levels of metabolites associated with the AA metabolic pathway, including 5,6-EET, 14,15-EET, phosphatidylcholine, and 20-HETE. Further experiments showed that SZF upregulated the expression of CYP4A and CYP2E proteins in renal tissue, as well as CYP2J and CYP2B proteins. Additionally, SZF significantly reduced the expression of inflammatory factors in renal tissue, enhanced antioxidant enzyme activity, and alleviated oxidative stress.
SZF exerts anti-inflammatory and antioxidant effects by regulating CYP450-mediated AA metabolism, leading to improved renal function and improved pathological state in DN mice.
糖尿病肾病（DN）是糖尿病的主要并发症，其特征为进行性肾损伤和炎症反应。尽管已有研究探讨了DN的病理机制，但有效的治疗方案仍然有限。
评估肾浊方（SZF）对DN小鼠模型的治疗作用，并采用转录组学和代谢组学方法研究其潜在的分子机制。
通过高脂饮食联合链脲佐菌素（STZ）注射建立DN小鼠模型，随后进行SZF治疗。我们使用转录组学和代谢组学技术分析SZF对DN小鼠肾组织基因表达和代谢物谱的影响。此外，基于转录组学和非靶向代谢组学的研究结果，我们进一步评估SZF对细胞色素P450（CYP450）介导的花生四烯酸（AA）代谢途径相关因子表达的影响，及其对炎症和氧化应激的作用。
SZF干预显著降低了DN小鼠的高血糖水平，减轻了肾功能损害。病理分析显示，SZF治疗改善了肾组织损伤，减少了纤维化，并减少了糖原沉积。转录组学分析表明，SZF影响了CYP450相关基因的mRNA表达，包括 、 、 /、 、 、 和 。非靶向代谢组学结果表明，SZF改变了与AA代谢途径相关的代谢物水平，包括5,6-环氧二十碳三烯酸（5,6-EET）、14,15-环氧二十碳三烯酸（14,15-EET）、磷脂酰胆碱和20-羟基二十碳四烯酸（20-HETE）。进一步实验表明，SZF上调了肾组织中CYP4A和CYP2E蛋白的表达，以及CYP2J和CYP2B蛋白的表达。此外，SZF显著降低了肾组织中炎症因子的表达，增强了抗氧化酶活性，减轻了氧化应激。
SZF通过调节CYP450介导的AA代谢发挥抗炎和抗氧化作用，从而改善DN小鼠的肾功能和病理状态。
