PPARα激动剂WY14643对大鼠应激性肝损伤的保护作用

Protective effect of PPARα agonist WY14643 on stress-induced liver injury in rats

目的:探讨过氧化物酶体增殖物激活受体α(PPARα)激动剂WY14643对应激性肝损伤的保护作用。方法:将14只雌性SD大鼠随机分为2组:对照组(NC)和模型组(SLI),每组各7只,采用水浸束缚法建立应激性肝损伤模型,造模21 d后,HE染色法观察肝脏组织形态学变化,酶联免疫吸附测定法(ELISA法)测定血清皮质酮(CORT)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、肿瘤坏死因子α(TNF-α)、白细胞介素-1β(IL-1β)、总胆固醇(TC)、三酰甘油(TG)含量,转录组测序技术寻找对照组和模型组的差异表达基因,并通过荧光定量PCR(qRT-PCR)对差异表达基因进行验证。选择差异表达基因PPARα激动剂WY14643,将24只SD大鼠随机分为对照组、模型组、WY14643低剂量组(WYL)和WY14643高剂量组(WYH),在每天束缚应激前1 h, WYL和WYH组分别腹腔注射0.5和1 mg·kg-1的WY14643,对照组和模型组腹腔注射等剂量生理盐水,通过水浸束缚应激实验观察WY14643是否具有抗应激性肝损伤的保护作用及分子机制。结果:ELISA结果显示WY14643可减少大鼠血清CORT,ALT,AST,TNF-α,IL-1β,TC和TG含量。肝脏HE染色结果显示,WY14643能减轻应激产生的肝脏损伤。Western Blot结果显示,WY14643可降低大鼠肝脏PI3K,AKT和NF-κB的蛋白表达。结论:WY14643能改善水浸束缚应激所致的肝损伤,且该作用可能与其抑制PI3K/AKT/NF-κB通路有关。

Objective: To investigate the protective effect of PPARα agonist WY14643 on stress-induced liver injury. Methods: Fourteen female SD rats were randomly divided into control group(NC) and model group(SLI), 7 in each group. The stress-induced liver injury model was established by the water immersion restraint method. After 21 days of modeling, the morphological changes of liver tissue were observed by HE staining method, serum corticosterone(CORT), alanine transaminase(ALT), aspartate aminotransferase(AST), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), total cholesterol(TC), triglyceride(TG) contents were measured by ELISA method, transcriptome sequencing technology was used to find the differentially expressed genes between control group and model group, and qRT-PCR was used to verify the differentially expressed genes. The differentially expressed gene PPARα agonist WY14643 was selected, and 24 SD rats were randomly divided into control group, SLI, WY14643 low-dose group(WYL) and WY14643 high-dose group(WYH). One hour before the daily restraint stress, WYL and WYH groups were intraperitoneally injected with 0.5 and 1 mg·kg-1 of WY14643, respectively. The control group and model group were intraperitoneally injected with the equal doses of saline, and water immersion restraint stress experiment was performed to observe whether WY14643 has anti-stress protective effect and molecular mechanism of liver injury. Results: ELISA results showed that WY14643 could reduce rat serum CORT, ALT, AST, TNF-α, IL-1β, TC, TG contents. The results of liver HE staining showed that WY14643 could reduce liver damage caused by stress. Western blot results showed that WY14643 could reduce the protein expression of PI3 K, AKT and NF-κB in rat liver. Conclusion: WY14643 can improve the liver damage caused by water immersion restraint stress, and this effect may be related to its inhibition of PI3 K/AKT/NF-κB pathway.