桂枝提取物对AS大鼠IL-6/STAT3信号通路的影响分析

Analysis the impaction of Guizhi extraction on AS rat IL-6/STAT3 signaling pathway

目的:分析桂枝提取物对动脉粥样硬化(AS)大鼠白细胞介素-6(IL-6)/信号转导子和转录活化子3(STAT3)信号通路的影响。方法:选取健康纯种SD雄性大白鼠共366只,随机分为正常对照组、模型组和桂枝对照组。采用实时荧光定量PCR技术检测AS大鼠腹主动脉血管AGTRl、IL-6 m RNA的表达;采用Western blotting检测TLR4、LXR、NF-κB P65/p-NF-κB P65、JNK/P-JNK、JAK1/p-JAK1、STAT3/p-STAT3、P38 MAPK/p-P38MAPK、IL-6在AS大鼠腹主动脉中的表达;ELISA法检测ERK1/2/P-ERK1/2在大鼠腹主动脉中的表达。结果:与正常对照组比较,模型组腹主动脉血管IL-6表达明显升高(P<0.05);与模型组比较,桂枝对照组IL-6的水平显著降低(P<0.05)。模型组腹主动脉p-JAK1水平与正常对照组比较,升高显著,同时p-STAT3水平显著降低(P<0.05);桂枝对照组p-JAK1水平与模型组比较,显著降低(P<0.05);而p-STAT3水平显著升高(P<0.05)。结论:桂枝提取物可以通过降低TLR4和TLR4 m RNA水平,升高LXR和LXR m RNA水平,同时抑制JNK、p38 MAPK和ERK1/2的磷酸化,作用于NFκB转录因子,抑制IL-6分泌,进而影响JAK2/STAT3信号转导通路。

Objective： To analyze Guizhi extraction to affect athcrosclerosis （AS） composition of the atherosclerotic rat interleukin-6/signal transducer and activator of transcription 3 （IL-6/STAT3） signaling pathway. Methods： Healthy purebred total 366 male SD rats were randomly divided into normal control group, model group and Guizhi control group. Using real-time quantitative PCR to detect AGTR1, IL-6 mRNA expression in rat. Using Western blotting to detect TLR4, LXR, NF-κB P65/p-NF- κB P65, JNK/P-JNK, JAK1/p-JAK1, STAT3/p-STAT3, P38 MAPK/p-P38 MAPK, IL-6 expression in the abdominal aorta of rats; Using ELISA assay to detect ERK1/2/P-ERK1/2 expression in the abdominal aorta of rats. Results： Compared with normal control group, the model group vascular IL-6 expression was significantly increased in abdominal aorta （P〈0.05）; the level of Guizhi group IL-6 were significantly reduced compared with the model group （P〈0.05）. The expression of abdominal aortic IL-6 mRNA of model group was significantly increased （P〈0.05）; compared with the model group, significantly lower IL-6 mRNA expression Guizhi group （P〈0.05）. With the normal control group, model group blank abdominal aortic p-JAK1 levels significantly increased, p-STAT3 levels were significantly lower （P〈0.05）; Guizhi group p-JAK1 levels were significantly reduced, p-STAT3 levels were significantly increased （P〈0.05）. Conclusion： The extract of Guizhi could reduce levels of TLR4 and TLR4 mRNA, increase LXR and the LXR mRNA levels, while suppress JNK, phosphorylation of p38 MAPK and ERK1/2, and act on the NF-κB transcription factor and inhibit IL-6 secretion, thereby affec JAK2/STAT3 signal transduction pathway.