Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Beijing Tcmages Pharmaceutical Co., LTD, Beijing, PR China.
Phytomedicine. 2018 Oct 1;49:52-65. doi: 10.1016/j.phymed.2018.05.019. Epub 2018 Jun 7.
Obese subjects have been considered to be in a state of chronic, low-grade systemic inflammation. Excess fat accumulation and persistent inflammation may promote renal dysfunction, to cause chronic kidney disease (CKD) and even end-stage kidney failure. Coptidis Rhizoma is a classical traditional Chinese herb well known for its hypoglycemic and hypolipidemic properties. The mechanism is partially associated with its anti-inflammatory effect. However, this effect is rarely investigated in obesity and obesity-related glomerulopathy (ORG).
The current study was designed to evaluate the effect of Coptidis Rhizoma on ORG. It also aimed to determine whether this renal protection effect of Coptidis Rhizoma was related to the inhibition of NLRP3 inflammasome in ORG.
Coptidis Rhizoma concentrated granules were prepared and the main components were identified by 3D-High Performance Liquid Chromatography (3D-HPLC) assay. The animal model of early stage ORG was established in obesity-prone (OP) rats by high protein and high fat diet feeding for 12 weeks. The treatment with Coptidis Rhizoma at different dosages was administered by intragastric infusion simultaneously. Then body weight, kidney weight, plasma lipid profiles, 24 h urine protein/albumin content and kidney histology were measured. Inflammatory biomarkers were examined both in the rat plasma and renal cortex. The gene expressions of NLRP3 inflammasome complex and NF-κB in renal tissues were also measured.
Coptidis Rhizoma alleviated dyslipidemia and reduced the renal weight of the rats with ORG. Meanwhile, urinary albumin to creatinine ratio and creatinine clearance rate were significantly improved. Coptidis Rhizoma also attenuated glomerular hypertrophy, mesangial hyperplasia, and effacement of podocyte foot in renal tissues of ORG rats. In addition, Coptidis Rhizoma intervention decreased the levels of proinflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-18) both in plasma and renal tissue. The gene expression of NLRP3 inflammasome was down-regulated and NF-κB activity was also inhibited by Coptidis Rhizoma in renal tissues of ORG rats.
Coptidis Rhizoma can ameliorate early renal damage in ORG rats and the mechanisms appear to be related to the inhibition of NLRP3 inflammasome complex.
肥胖受试者被认为处于慢性、低度全身炎症状态。脂肪过度堆积和持续的炎症可能会导致肾功能障碍，引起慢性肾脏病（CKD）甚至终末期肾衰竭。黄连是一种经典的传统中药，以其降血糖和降血脂特性而闻名。其机制部分与抗炎作用有关。然而，这种作用在肥胖和肥胖相关性肾小球病（ORG）中很少被研究。
本研究旨在评估黄连对 ORG 的作用。还旨在确定黄连对 ORG 的肾脏保护作用是否与 NLRP3 炎性体的抑制有关。
制备黄连浓缩颗粒，并通过三维高效液相色谱法（3D-HPLC）测定其主要成分。通过高脂高蛋白饮食喂养肥胖易感（OP）大鼠 12 周建立早期 ORG 动物模型。同时通过灌胃给予黄连不同剂量的治疗。然后测量体重、肾重、血浆脂质谱、24 小时尿蛋白/白蛋白含量和肾脏组织学。检测大鼠血浆和肾皮质中的炎症生物标志物。还测量了肾组织中 NLRP3 炎性体复合物和 NF-κB 的基因表达。
黄连缓解了 ORG 大鼠的血脂异常，并减轻了其肾脏重量。同时，尿白蛋白与肌酐比值和肌酐清除率显著改善。黄连还减轻了 ORG 大鼠肾脏组织中的肾小球肥大、系膜增生和足细胞足突融合。此外，黄连干预降低了血浆和肾组织中促炎细胞因子（TNF-α、IL-1β、IL-6 和 IL-18）的水平。黄连还下调了 NLRP3 炎性体在 ORG 大鼠肾组织中的基因表达，并抑制了 NF-κB 的活性。
黄连可改善 ORG 大鼠的早期肾脏损伤，其机制可能与抑制 NLRP3 炎性体复合物有关。
