Yang Hongling, Wu Shukun
Department of Nephrology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital No. 23, Section 2, 1st Ring Road (West) Chengdu Sichuan 610000 China
Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital Chengdu Sichuan 610000 China.
RSC Adv. 2018 Jun 13;8(39):21816-21822. doi: 10.1039/c8ra01674g.
: Diabetic nephropathy (DN) is a major cause of chronic kidney disease around the world. Endoplasmic reticulum (ER) stress plays an important role in DN progression. Ligustrazine (Lig) is derived from the Chinese herb and is reported to exert anti-oxidant, anti-inflammation and anti-fibrosis effects. The aim of our study was to investigate the influence of Lig on the treatment of DN. : Streptozotocin (STZ) was used to induce diabetes in Sprague-Dawley (SD) rats. Then, STZ-induced rats were treated with different concentrations of Lig (50 or 150 mg kg day) for 8 weeks of treatment. Urinary albumin concentrations, blood urea nitrogen (BUN), serum creatinine (Scr) and creatinine clearance (Ccr) were determined. The levels of proinflammatory cytokines (IL-8, IL-6, IL-1β and TNF-α) were estimated by ELISA. TUNEL assay was used for apoptosis index measurement. Western blot was used for the detection of GRP78, CHOP, p-eIF2α, eIF2α, p-p38, p-38, p-ERK1/2 and ERK1/2. : Lig treatment significantly reduced urinary albumin excretion, BUN and Scr and increased Ccr in STZ-induced rats. Lig also suppressed the levels of IL-8, IL-6, IL-1β and TNF-α and inhibited apoptosis dose-dependently. In addition, Lig inhibited GRP78 and CHOP expression and prevented the phosphorylation of eIF2α, p-38 and ERK1/2. : Our study indicated that Lig attenuated renal damage by inhibiting ER stress in DN by inactivating MAPK pathways.
糖尿病肾病(DN)是全球慢性肾脏病的主要病因。内质网(ER)应激在DN进展中起重要作用。川芎嗪(Lig)源自中药,据报道具有抗氧化、抗炎和抗纤维化作用。我们研究的目的是探讨Lig对DN治疗的影响。用链脲佐菌素(STZ)诱导Sprague-Dawley(SD)大鼠患糖尿病。然后,用不同浓度的Lig(50或150mg/kg·天)对STZ诱导的大鼠进行8周治疗。测定尿白蛋白浓度、血尿素氮(BUN)、血清肌酐(Scr)和肌酐清除率(Ccr)。通过酶联免疫吸附测定(ELISA)评估促炎细胞因子(IL-8、IL-6、IL-1β和TNF-α)的水平。采用末端脱氧核苷酸转移酶介导的缺口末端标记法(TUNEL)检测凋亡指数。用蛋白质免疫印迹法检测葡萄糖调节蛋白78(GRP78)、C/EBP同源蛋白(CHOP)、磷酸化真核细胞起始因子2α(p-eIF2α)、真核细胞起始因子2α(eIF2α)、磷酸化p38丝裂原活化蛋白激酶(p-p38)、p38丝裂原活化蛋白激酶(p-38)、磷酸化细胞外信号调节激酶1/2(p-ERK1/2)和细胞外信号调节激酶1/2(ERK1/2)。Lig治疗显著降低了STZ诱导大鼠的尿白蛋白排泄、BUN和Scr,并增加了Ccr。Lig还剂量依赖性地抑制IL-8、IL-6、IL-1β和TNF-α水平并抑制细胞凋亡。此外,Lig抑制GRP78和CHOP表达,并阻止eIF2α、p-38和ERK1/2的磷酸化。我们的研究表明,Lig通过使丝裂原活化蛋白激酶(MAPK)通路失活来抑制DN中的内质网应激,从而减轻肾脏损伤。