胰高糖素样肽-1受体激动剂通过JNK信号通路促进肝星形细胞凋亡的机制研究  

The role of glucagon-like peptide-1 receptor agonist on the promotion of hepatic stellate cell apoptosis through JNK signaling pathway

作　　者：李桃红 贺晓敏[2] 刘英超[2] 杨育林[2] 唐翠兰[2] 吴凌康[2] 

机构地区：[1]浙江省宁波市医疗中心李惠利东部医院ICU,315000 [2]浙江中医药大学附属第二医院老年医学科,杭州310005

出　　处：《国际流行病学传染病学杂志》2017年第3期167-170,共4页International Journal of Epidemiology and Infectious Disease

基　　金：浙江省医药卫生科技计划（2017KY121）

摘　　要：目的探讨胰高糖素样肽-1受体激动剂（GLP-1RA）通过JNK信号通路促进肝星形细胞（HSC）凋亡的机制。方法体外培养人HSC并进行形态学鉴定，将HSC样本随机分成对照组（20份）、GLP-1RA组（20份）和JNK阻断组（20份）。对照组HSC在常规培养基础上加入高糖（终浓度25mmol／L），GLP-1RA组在对照组基础上加入GLP．1RA利拉鲁肽（终浓度10mmol／L），JNK阻断组在GLP-1RA组基础上加入JNK信号通路阻断剂SP600125（终浓度20μmol／L）进行培养；培养120h后用流式细胞术检测各组的HSC凋亡情况。同时采用Western印迹法检测各组的p-JNK蛋白表达水平。结果三组的平均凋亡率和平均P—JNK的表达水平差异均有统计学意义（F=19．412和66．451，P均〈0．01）。GLP-1RA组的凋亡率和p-JNK蛋白表达水平分别为（30．61±4．07）％和（22．79±3．80）％，均高于对照组，差异均具有统计学意义（t=0．530和9．854，P均〈0．01）；JNK阻断组的细胞凋亡率和p-JNK蛋白表达水平分别为（23．48±4．41）％和（10．66±4．15）％，均低于GLP-1RA组，差异有统计学意义（t=-5．428和-8．757，P均〈O．01）。结论JNK信号通路在GLP-1RA介导的HSC凋亡中起着关键作用，GLP．1RA可以通过JNK信号通路促成经高糖诱导活化的HSC发生凋亡。Objective To explore the mechanism of glucagon-like peptide-1 receptor agonist （GLP-1RA） promoting the apoptosis of hepatic stellate cells （HSC） through the JNK signaling pathway. Methods The HSC were cultured in vitro and applied morphological identification. HSC samples were divided into control group （20 samples）, GLP-1RA group （20 samples） and JNK signaling pathway blocking group （20 samples）. The control group was cultured with high glucose （final concentration of 25 retool/L）. The GLP-1RA group was added GLP- 1RA-Liraglutide （final concentration of 10 mmol/L） based on the control group. The JNK blocking group was added JNK signaling pathway blocker SP600125 （final concentration of 20 μmol/L） based on the GLP-1RA group. After 120 hours, the apoptosis of HSC in each group was detected by flow cytometry. The expression levels of p-JNK protein were determined by Western blotting. Results The differences of apoptosis rates of HSC and the expression levels of p-JNK protein in three group were statistically significant （F=19.412 and 66.451, P both 〈 0.01）. The apoptosis rate of HSC and the expression level of p-JNK protein in GLP-1RA group were （30.61±4.07）% and （22.79±3.80）%, which were both higher than control group with significant differences （t=0.530 and 9.854, P both 〈0.01）. The apoptosis rate of HSC and the expression level of p-JNK protein in JNK signaling pathway blocking group were （23.48±4.41）% and （10.66±4.15）%, which were both lower than GLP-1RA group with significant differences （t=-5.428 and -8.757, P both 〈0.01）. Conclusions JNK signaling pathway plays a key role in the GLP-1RA mediated apoptosis of HSC. GLP-1RA can promote the apoptosis of high glucose- induced HSC through JNK signaling pathway.

关 键 词：细胞凋亡 肝星形细胞 JNK信号通路 

分 类 号：R575.2[医药卫生—消化系统]