mangostin and Glomerulosclerosis--Focal-Segmental

To observe the protective effect of alpha-mangostin (α-MG) on focal segmental glomurular sclerosis (FSGS) induced by adriamycin.
 Methods: Adriamycin nephropathy (AN) model was induced by adriamycin (10 mg/kg) via a tail vein. Then the mice were treated with α-MG (12.5 mg/kg) or normal salin once daily for 6 weeks. At the end of 6 weeks, the mice were sacrificed, and the kidneys and blood samples were collected. Histopathology of the kidneys were analyzed under the optical microscope. The serum levels of biochemical indicators, such as serum creatinine (SCr), blood urea nitrogen (BUN) and cholesterol were determined. The levels of superoxide anion, malondialdehyde (MDA), and glutathione (GSH), the activity of superoxide dismutase (SOD) and catalase (CAT) in kidney tissues were determined. Serum levels of IL-1β, IL-18, IL-10 and adiponectin were determined. The levels of TGF-β1, collagen I (Col I), α-SMA, silent information regulator 1 (Sirt1) and the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) in kidney tissues were determined using immunohistochemical staining, Western blot, and RT-PCR.
 Results: The levels of SCr, proteinuria, urine protein to creatinine ratio and serum cholesterol were attenuated in AN mice after α-MG treatment, while creatinine clearance rate and serum albumin were upregulated (P<0.05). α-MG treatment alleviated the glomerular and interstitial fibrosis, downregulated the expression of fibrosis markers, such as Col I and α-SMA (P<0.05). α-MG treatment reduced the production of superoxide anion, the levels of MDA and GSH, and increased the activity of CAT and SOD (P<0.05). α-MG treatment inhibitd the generation of pro-inflammatory cytokines, such as IL-1β and IL-18 and promoted the production of anti-inflammatory cytokines, such as the IL-10 and adiponectin (P<0.05); α-MG treatment promoted the expression of Sirt1, inhibitd the expression of NLRP3 in kidney tissues (P<0.05).
 Conclusion: α-MG could attenuates FSGS of mice induced by adriamycin ameliorate and improve renal function. α-MG exerts its anti-inflammatory and anti-oxidative effects by up-regulation the expression of Sirt1 and suppression of NLRP3.. 目的：观察α-倒捻子素(alpha-mangostin，α-MG)治疗对阿霉素诱导的局灶节段性肾小球硬化(focal segmental glomurular sclerosis，FSGS)的肾脏保护作用。方法：BALB/c小鼠尾静脉注射阿霉素(10 mg/kg)诱导阿霉素肾病(adriamycin nephropathy，AN)模型后分为两组：1)AN+生理盐水组，用生理盐水灌胃；2)AN+α-MG组，用α-MG(12.5 mg/kg)灌胃。灌胃每日1次，从阿霉素注射当日开始。另取10只小鼠作为对照组。6周后处死小鼠，在光学显微镜下观察肾组织病理学改变；检测血肌酐(SCr)、血尿素氮(BUN)、血胆固醇等肾功能相关生化指标水平；检测肾组织中超氧阴离子，丙二醛(MDA)和谷胱甘肽(GSH)水平以及超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性；检测血清中IL-1β，IL-18，IL-10，脂联素水平；用免疫组织化学、RT-PCR和Western印迹检测肾组织中TGF-β1，I型胶原蛋白(collagen I，Col I)，α-SMA，沉默信息调控因子1(silent information regulator 1，Sirt1)，核苷酸结合结构域样受体蛋白3(NLRP3)水平。结果：α-MG治疗可降低AN小鼠血肌酐、蛋白尿、尿蛋白/尿肌酐、血胆固醇，增加肌酐清除率、血浆白蛋白(P<0.05)；缓解肾小球硬化和间质纤维化；下调纤维化指标Col I和α-SMA的表达(P<0.05)；减少肾组织超氧阴离子的产生，降低MDA和GSH水平以及增加CAT和SOD活性(P<0.05)；降低血清炎性因子IL-1β和IL-18水平，升高抗炎因子IL-10和脂联素水平(P<0.05)；促进肾组织中Sirt1表达，抑制NLRP3的表达(P<0.05)。结论：α-MG治疗能够改善阿霉素诱导的FSGS小鼠肾功能，延缓肾小球硬化和间质纤维化进程。α-MG通过促进肾脏Sirt1表达和抑制NLRP3表达而发挥抗炎和抗氧化作用。.

Topics: Animals; Disease Models, Animal; Doxorubicin; Glomerulosclerosis, Focal Segmental; Kidney; Mice; Mice, Inbred NOD; Protein Kinase Inhibitors; Xanthones