Zhang Qian, Xiao Xinhua, Li Ming, Yu Miao, Ping Fan
Key Laboratory of Endocrinology, Department of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Front Pharmacol. 2022 Aug 25;13:915592. doi: 10.3389/fphar.2022.915592. eCollection 2022.
Diabetic nephropathy (DN) is a severe diabetic complication of the kidney and is the main cause of end-stage kidney disease worldwide. () is not only a traditional Chinese medicine (TCM) but also a healthy food. In China, has been widely used to treat various kidney diseases. Bailing Capsule, which active ingredient is , is approved to treat kidney disease, respiratory disease, and immune disease. However, its underlying mechanism in DN remains unclear. The purpose of the present study was to investigate the underlying mechanism of Bailing Capsule on kidney in diabetic rats. The DN model was established by streptozotocin (STZ) injection. Low and high doses of Bailing Capsule were orally administrated for 12 weeks after diabetes induction. Renal function was evaluated by serum creatinine, blood urea nitrogen, 24-h urinary protein, and urinary albumin. Mesangial matrix expansion and renal fibrosis were measured using histopathology staining. We found that the disorder of renal function and pathology in DN rats was significantly modified by Bailing Capsule treatment. Consistently, Bailing Capsule markedly alleviated DN rat glomerulosclerosis, tubulointerstitial injury and renal fibrosis as shown by pathological staining. Moreover, Bailing Capsule significantly reduced the kidney triglyceride content and renal lipid droplet formation in DN rats. The renal transcriptome revealed that Bailing Capsule-treated kidneys had 498 upregulated genes and 448 downregulated genes. These differentially expressed genes were enriched in the peroxisome proliferator activated receptor (PPAR) pathway and fatty acid metabolism function ontology. mRNA and protein expression analyses revealed substantial enhancement of the lipolysis pathway and inhibition of lipogenesis in Bailing Capsule-treated rat kidneys compared to DN rats. Bailing Capsule activated the expression of PPARα, ACOX1 (acyl-CoA oxidase 1), and SCD (stearoyl-CoA desaturase) in diabetic nephropathy while suppressing the expression of FASN (fatty acid synthase). In conclusion, Bailing Capsule could attenuate renal triglyceride accumulation in diabetic rats by moderating PPARα pathway.
糖尿病肾病(DN)是一种严重的糖尿病肾脏并发症,是全球终末期肾病的主要原因。(此处原文有缺失信息)不仅是一种中药,也是一种健康食品。在中国,(此处原文有缺失信息)已被广泛用于治疗各种肾脏疾病。以(此处原文有缺失信息)为活性成分的百令胶囊被批准用于治疗肾脏疾病、呼吸系统疾病和免疫疾病。然而,其在糖尿病肾病中的潜在机制仍不清楚。本研究的目的是探讨百令胶囊对糖尿病大鼠肾脏的潜在作用机制。通过注射链脲佐菌素(STZ)建立糖尿病肾病模型。糖尿病诱导后,口服低剂量和高剂量的百令胶囊,持续12周。通过血清肌酐、血尿素氮、24小时尿蛋白和尿白蛋白评估肾功能。使用组织病理学染色测量系膜基质扩张和肾纤维化。我们发现,百令胶囊治疗可显著改善糖尿病肾病大鼠的肾功能紊乱和病理状态。同样,病理染色显示百令胶囊显著减轻了糖尿病肾病大鼠的肾小球硬化、肾小管间质损伤和肾纤维化。此外,百令胶囊显著降低了糖尿病肾病大鼠肾脏的甘油三酯含量和肾脂滴形成。肾脏转录组显示,经百令胶囊治疗的肾脏有498个上调基因和448个下调基因。这些差异表达基因富集在过氧化物酶体增殖物激活受体(PPAR)途径和脂肪酸代谢功能本体中。mRNA和蛋白质表达分析显示,与糖尿病肾病大鼠相比,经百令胶囊治疗的大鼠肾脏中脂解途径显著增强,脂肪生成受到抑制。百令胶囊在糖尿病肾病中激活了PPARα、ACOX1(酰基辅酶A氧化酶1)和SCD(硬脂酰辅酶A去饱和酶)的表达,同时抑制了FASN(脂肪酸合酶)的表达。总之,百令胶囊可通过调节PPARα途径减轻糖尿病大鼠肾脏甘油三酯的积累。