Curcumin reduces the risk of chronic kidney damage in mice with nonalcoholic steatohepatitis by modulating endoplasmic reticulum stress and MAPK signaling
Curcumin reduces the risk of chronic kidney damage in mice with nonalcoholic steatohepatitis by modulating endoplasmic reticulum stress and MAPK signaling
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DOI：
10.1016/j.intimp.2017.05.035
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发表时间：
2017-08-01
影响因子：
5.6
通讯作者：
Watanabe, Kenichi
中科院分区：
文献类型：
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作者：
Afrin, Rejina;Arumugam, Somasundaram;Watanabe, Kenichi
发展证实建议，在动态型NAFLD患者中，特别是非酒精性脂肪性肝炎（NASH）可能具有肾脏损害进展的致病部分。在这项研究中，我们研究了姜黄素对NASH引起的慢性肾损伤（CKD）的影响及其可能的机制。为了制备该NASH模型，将新生C57 BL/6 J雄性小鼠暴露于低剂量链脲佐菌素（STZ），并在4周龄时喂食高脂饮食（HFD），并持续至14周龄，在STZ注射10周后，每天通过口服管饲法给予100 mg/kg剂量的姜黄素，并持续沿着HFD喂食4周。NASH诱发的小鼠表现出肾毒性，如通过肾容量下降所证明的，这通过测量血清中的血尿素氮和肌酐以及与正常的组织病理学变化来评估。这些进展被姜黄素治疗所改变，这带来了肾容量的巨大变化。此外，姜黄素显著降低NAD（P）H氧化酶亚基（p67 phox、p47 phox、p22 phox）、硝基酪氨酸和CYP 2 E1肾蛋白表达以及降低促炎细胞因子表达（TNF α、IL-1 β、IFN γ）。在NASH诱导的小鼠中，有丝分裂原活化蛋白激酶（MAPK）（p-JNK、p-ERK 1/2）和葡萄糖调节蛋白78、CHOP的肾蛋白表达增加，姜黄素治疗减弱了这些增加的表达。此外，姜黄素治疗还降低了NASH肾脏中的凋亡信号蛋白（裂解的caspase-3，裂解的caspase-12）。总之，我们的结果表明，姜黄素保护肾功能，可能是通过减弱ER应激介导的MAPK信号转导。
Developing confirmation recommends that in patients with dynamic type of NAFLD, particularly nonalcoholic steatohepatitis (NASH) may have the pathogenic parts in the advancement of kidney damage. In this study we have examined the impact of curcumin on NASH instigated chronic kidney damage (CKD) and the putative mechanisms. To prepare this NASH model, neonatal C57BL/6J male mice were exposed to low -dose streptozotocin (STZ) and were fed high-fat diet (HFD) at the age of 4 weeks and continued up to 14 weeks, curcumin was given at 100 mg/kg dose by oral gavage daily after 10 weeks of STZ injection and continued for 4 weeks along with HFD feeding. NASH incited mice demonstrated nephrotoxicity as proved by declining renal capacity, which was evaluated by measuring blood urea nitrogen and creatinine in serum and histopathological variations from the norm. These progressions were switched by curcumin treatment, which brought about huge change in renal capacity. Furthermore, curcumin markedly decreased NAD(P)H oxidase subunits (p67phox, p47phox, p22phox), nitrotyrosine and CYP2E1 renal protein expression as well as reduced pro -inflammatory cytokine expression (TNF alpha, IL-1 beta, IFN gamma). Renal protein expression of mitogen activated protein kinases (MAPKs) (p-JNK, p-ERK1/2) and glucose regulated protein 78, CHOP were increased in NASH induced mice and curcumin treatment attenuated these increased expressions. In addition, curcumin treatment also decreased the apoptosis signaling proteins (cleaved caspase-3, cleaved caspase-12) in the NASH kidney. Taken together, our results suggest that curcumin preserves the renal function, probably by attenuating the ER stress mediated MAPK signaling.