桂枝提取物对动脉粥样硬化大鼠白细胞介素6/信号转导子和转录活化子3信号通路的影响

Impact Guizhi extract on IL-6/STAT3 signaling pathway in atherosclerotic rats

摘要:

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/信号转导子和转录活化子3（IL-6/
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、空白AS模型组和桂枝提取物组。免疫组织化学法检测Toll样受体4（TLR4）、肝脏X受体（LXR）、C-Jun的N末端激酶（JNK/P-JNK）、细胞外调节蛋白激酶（ERK1/2/P-ERK1/2）、P38丝裂原活化蛋白激酶（P38MAPK/p-P38MAPK）、白细胞介素6（IL-6）、蛋白质酪氨酸激酶JAK-1抗原（JAK1/p-JAK1）、转录活化子3（STAT3/p-STAT3）及核转录因子kappa B（NF-κB）P65的表达在AS大鼠腹主动脉中的表达；用实时荧光定量PCR技术检测AS大鼠腹主动脉血管AGTRl mRNA和IL-6 mRNA的表达。结果  与正常对照组比较，空白模型组腹主动脉血管IL-6阳性表达率明显升高（P <0.05）；与空白模型组比较，桂枝提取物组IL-6的阳性表达率显著降低（P <0.05）。与正常对照组比较，空白模型大鼠腹主动脉血管IL-6 mRNA的表达显著升高（P <0.05）；与空白模型组比较，桂枝提取物组IL-6 mRNA的表达显著降低（P <0.05）。与正常对照组比较，空白模型组腹主动脉p-JAK1阳性表达率显著提高，p-STAT3阳性表达率显著降低（P <0.05）；与空白模型组比较，桂枝提取物组p-JAK1阳性表达率显著降低，p-STAT3阳性表达率显著升高（P <0.05）。结论  桂枝提取物可以通过降低TLR4水平，升高LXR水平，同时抑制JNK、p38MAPK和ERK1/2的磷酸化，作用于NF-κB转录因子，抑制IL-6分泌，进而影响JAK2/STAT3信号转导通路。

Abstract:

Objective To analyze effect of Guizhi extraction on the interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling pathway in atherosclerosis (AS) rats. Methods Totally 366 healthy purebred male SD rats were randomly divided into normal control group, blank AS model group and Guizhi extract group. Immunohistochemistry was used to detect TLR4, LXR, JNK/p-JNK, ERK1/2/P-ERK1/2, P38MAPK/p-P38MAPK, IL-6, JAK1/p-JAK1, STAT3/p-STAT3 and NFКB P65/ p-NFКB P65 expressions in rats with aortic AS. Real-time PCR was used to detect AGTRl mRNA and IL-6 mRNA expressions in abdominal aorta of AS rats. Results Compared with the normal control group, vascular IL-6 expression was significantly increased in  the abdominal aorta of the blank model group (P ＜ 0.05); compared with the blank model group, the level of IL-6 in the Guizhi extract group was significantly reduced (P ＜ 0.05). Compared with the normal control group, the positive IL-6 mRNA expression rate in the abdominal aorta was significantly increased in the blank model group (P ＜ 0.05). Compared with the blank model group, IL-6 mRNA expression was significantly lowered in the Guizhi extract group (P ＜ 0.05). Compared with the normal control group, abdominal aortic p-JAK1 level significantly increased, p-STAT3 level significantly lowered in the blank model group (P ＜ 0.05). Compared with the blank model group, p-JAK1 level significantly reduced and p -STAT3 level significantly increased in the Guizhi extract group (P ＜ 0.05). Conclusions Guizhi extract can inhibit IL-6 secretion, thereby affect JAK2/STAT3 signal transduction pathway by reducing TLR4 level, increasing LXR level while suppressing phosphorylation of JNK, p38MAPK and ERK1/2 and acting on the NFКB transcription factor.