Salubrinal通过 eIF2α信号通路治疗非酒精性脂肪肝 #br#

摘要：目的 探讨 Salubrinal对肥胖诱导的非酒精性脂肪肝的疗效。方法 选用 30只雌性 C57BL/6小鼠，随机分 为对照（SCD）组、高脂饮食（HF）组和高脂饮食治疗（HF+S）组。HF组和 HF+S组小鼠给予含脂量为 60%的高脂饮食， 4周肥胖诱导后，HF+S组接受 Salubrinal皮下注射 4周。实验过程中每周测量动物体成分变化，采取静脉血检测血脂 指标，收集皮下、内脏脂肪和肝脏进行湿质量测定。为探索 Salubrinal对肝脏的影响及作用机制，通过 HE、油红 O染 色观察肝脏病理改变，Western blot检测肝组织 eIF2α信号通路相关蛋白 Bip、p-eIF2α、eIF2α、ATF4和 CHOP的表达。 结果 与 SCD组比较，HF组小鼠的血脂水平和脂肪堆积明显增加，Salubrinal治疗后，脂质紊乱情况减轻。同时，肝 脏组织学检查显示，Salubrinal可以明显缓解肝脂肪变性严重程度并抑制异常脂质沉积。此外，Western blot分析表 明，Salubrinal 通过增加 Bip、p-eIF2α/eIF2α 和 ATF4 的表达量，降低 CHOP 的表达水平抑制内质网应激。结论 Salubrinal能够有效缓解肥胖和肝脂肪变性，并通过 eIF2α信号通路调控内质网应激而影响脂质代谢。

Salubrinal treats the non-alcoholic fatty liver disease through eIF2α signaling pathway #br#

Abstract: Objective To investigate the effect of salubrinal on obesity-induced non-alcoholic fatty liver disease. Methods Thirty female C57BL/6 mice were randomly divided into three groups: standard chow diet (SCD) group, high-fat diet (HF) group and HF with salubrinal (HF+S) group. The HF and HF+S groups were given a high-fat diet (fat content: 60%). After 4-week obesity induction, salubrinal was subcutaneously injected for the next 4 weeks in HF+S group. During the experiment, the changes in animal body compositions were measured regularly. Serum lipid parameters were examined through venous blood. The abdominal subcutaneous fat, periuterine and perirenal fat, and liver were collected for wet mass determination. The pathological changes of the liver tissues were observed by H&E and oil red O staining for investigating the effect and mechanism of salubrinal on the hepatic steatosis. The expressions of proteins related to eIF2α signaling (Bip, p-eIF2α, eIF2α, ATF4 and CHOP) were detected by Western blot assay. Results Compared to the SCD group, the serum lipid level and the fat accumulation were increased in HF and HF+S groups. After treatment with salubrinal, the lipid disorder was relieved. Also, the histological severity of hepatic steatosis in the liver was suppressed in response to salubrinal. In addition, Western blot analysis showed that salubrinal inhibited endoplasmic reticulum stress by increasing the expressions of Bip, p-eIF2α and ATF4 with a decrease level of CHOP. Conclusion Salubrinal can effectively alleviate obesity and non-alcoholic fatty liver disease and regulate lipid metabolism by altering endoplasmic reticulum stress through eIF2α signaling.