雷公藤多苷通过JAK2/STAT3信号通路减轻溃疡性结肠炎大鼠肠黏膜细胞凋亡及炎症的实验研究

Tripterygium glycosides attenuate intestinal mucosal apoptosis and inflammation in rats with ulcerative colitis through JAK2/STAT3 signaling pathway

目的 研究雷公藤多苷(TG)通过Janus激酶2(JAK2)/信号转导与转录激活子3(STAT3)信号通路对溃疡性结肠炎(UC)大鼠肠黏膜细胞凋亡及炎症的调节作用。方法将SD大鼠分为对照组、UC组、TG组、AG490组,UC组、TG组、AG490组采用三硝基苯磺酸/乙醇灌肠的方式建立UC模型,TG组给予TG灌胃干预,AG490组给予JAK2/STAT3抑制剂AG490干预。检测肠黏膜细胞凋亡率、凋亡基因及JAK2/STAT3表达、炎症细胞因子含量。结果UC大鼠肠黏膜细胞凋亡率、Caspase-9、Caspase-3、p-JAK2、p-STAT3的表达水平及TNF-α、IL-1β、IL-6的含量均明显高于对照组,Bcl-2、Bcl-xL的表达水平明显低于对照组(P<0.05);TG组大鼠肠黏膜细胞凋亡率、Caspase-9、Caspase-3、p-JAK2、p-STAT3的表达水平及TNF-α、IL-1β、IL-6的含量均明显低于UC组,Bcl-2、Bcl-xL的表达水平明显高于UC组(P<0.05)。AG490组大鼠肠黏膜细胞凋亡率、Caspase-9及Caspase-3的表达水平、TNF-α、IL-1β、IL-6的含量均明显低于UC组,Bcl-2、Bcl-xL的表达水平明显高于UC组(P<0.05)。结论TG能够通过JAK2/STAT3信号通路减轻UC大鼠肠黏膜细胞的凋亡及炎症。

Objective To investigate the effects of tripterygium glycosides (TG) on intestinal mucosal apoptosis and inflammation in rats with ulcerative colitis (UC) through Janus kinase 2 (JAK2)/signal transduction and activator of transcription 3 (STAT3) signaling pathway. Methods SD rats were divided into control group, UC group, TG group and AG490 group. UC group and TG group were treated with trinitrobenzene sulfonic acid/ethanol enema to establish UC model. TG group was given intragastric intervention of TG, AG490 group was given intervention by JAK2/STAT3 inhibitor AG490. Apoptotic rate, expression of apoptotic genes and JAK2/STAT3, the contents of inflammatory cytokines in intestinal mucosa were detected. Results The apoptotic rate, the expression levels of Caspase-9, Caspase-3, p- JAK2,p-STAT3 and the contents of TNF-a, IL-1β, IL-6 in intestinal mucosa of UC rats were significantly higher than those of control group, while the expression levels of Bcl-2 and Bcl-xL were significantly lower than those of control group ( P <0.05);the apoptotic rate, the expression levels of Caspase-9, Caspase-3, p- JAK2,p-STAT3 and the contents of TNF-a, IL-1β, IL-6 in intestinal mucosa of TG rats were significantly lower than those of UC rats, the expression levels of Bcl-2 and Bcl-xL in intestinal mucosa were significantly higher than those in UC group ( P <0.05);the apoptotic rate, Caspase-9 and Caspase-3 expression levels, TNF-a, IL-1β, IL-6 contents in intestinal mucosa of AG490 group were significantly higher than those of UC group, while the expression levels of Bcl-2 and Bcl-xL were significantly lower than those of UC group ( P <0.05). Conclusion TG can alleviate intestinal mucosal apoptosis and inflammation in UC rats through JAK2/STAT3 signaling pathway.