基于JAK2/STAT3信号通路探讨凉血和营方对血栓闭塞性脉管炎大鼠血管炎性损伤的改善作用  

Ameliorative effects of Liangxue Heying Formula on vascular inflammatory injury in a rat model of thromboangiitis obliterans via JAK2/STAT3 signaling pathway

作　　者：冯夏 王御震 祝艳丹 赵诚 李骥 曹烨民 FENG Xia;WANG Yu-zhen;ZHU Yan-dan;ZHAO Cheng;LI Ji;CAO Ye-min(Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Shanghai Traditional Chinese Medicine-Integrated Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200082,China)

机构地区：[1]上海中医药大学,上海201203 [2]上海中医药大学附属上海市中西医结合医院,上海200082

出　　处：《中成药》2024年第9期2915-2922,共8页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金项目(82174382,82104486);国家科技重大专项(2019ZX09201004-002-091);上海市2020年度科技创新行动计划项目(20Z21900200);上海市十三五临床重点专科(中医外科)(2019)。

摘　　要：目的研究凉血和营方对血栓闭塞性脉管炎(TAO)大鼠血管炎性损伤的影响。方法将大鼠随机分为假手术组、模型组和凉血和营方低、中、高剂量组(2.25、4.5、9 g/kg),大鼠后肢股动脉注射0.1 mL月桂酸钠(10 mg/mL)建立TAO大模型,造模成功后灌胃给予相应剂量药物。观察患肢形态变化并进行评级;使用激光多普勒血流仪扫描各组大鼠后肢血流量变化;ELISA法检测血浆TNF-α、IL-6、ICAM-1、VCAM-1水平;HE染色观察股动脉和股静脉组织病理变化;Western blot法检测股动脉组织中TNF-α、IL-6、JAK2、p-JAK2、STAT3、p-STAT3、ICAM-1、VCAM-1蛋白表达。结果与假手术组比较,模型组大鼠患肢形态学评分升高(P<0.01);患侧/健侧血液灌注量比降低(P<0.01);血浆TNF-α、IL-6、ICAM-1、VCAM-1水平升高(P<0.01);股动脉及股静脉组织中存在富含大量炎性细胞的血栓浸润,股动脉组织中TNF-α、IL-6、p-JAK2、p-STAT3、ICAM-1、VCAM-1蛋白表达升高(P<0.01)。与模型组比较,凉血和营方中、高剂量组大鼠患肢形态学评分降低(P<0.01),患侧/健侧血液灌注量比升高(P<0.01),股动脉及股静脉组织中血栓和炎性细胞浸润减少,股动脉组织中IL-6、p-STAT3蛋白表达降低(P<0.01);各剂量组血浆TNF-α、IL-6、ICAM-1、VCAM-1水平降低(P<0.05,P<0.01),股动脉组织中TNF-α、ICAM-1、VCAM-1、p-JAK2蛋白表达降低(P<0.01)。结论凉血和营方可以改善TAO大鼠全身炎症状态,抑制内皮细胞活化,减轻血管炎性损伤,其作用机制可能与调控JAK2/STAT3信号通路有关。AIM To study the effects of Liangxue Heying Formula on vascular inflammatory injury in a rat model of thromboangiitis obliterans(TAO).METHODS The rats were randomly divided into the sham operation group,the model group and the low,medium and high dose Liangxue Heying Formula groups(2.25,4.5,9 g/kg).With the rat TAO model successfully established by injection of 0.1 mL sodium laurate(10 mg/mL)into the femoral artery of hind limbs,corresponding doses of drugs by gavage were administered upon the rats.Subsequently,the rats had their morphological changes of the affected limbs observed and assessed;their changes of blood flow in hind limbs scanned by laser Doppler flowmetry;their plasma levels of TNF-α,IL-6,ICAM-1 and VCAM-1 detected by ELISA;their histopathological changes of femoral artery and vein observed by HE staining;and their protein expressions of TNF-α,IL-6,JAK2,p-JAK2,STAT3,p-STAT3,ICAM-1 and VCAM-1 in femoral artery detected by Western blot.RESULTS Compared with the sham operation group,the model group displayed increased morphological score of the affected limb(P<0.01);decreased blood perfusion ratio of the affected side/healthy side(P<0.01);increased plasma levels of TNF-α,IL-6,ICAM-1 and VCAM-1(P<0.01);more existence of thrombotic infiltration containing a larger number of inflammatory cells in femoral artery and femoral vein tissue,and increased protein expressions of TNF-α,IL-6,p-JAK2,p-STAT3,ICAM-1 and VCAM-1 in femoral artery(P<0.01).Compared with the model group,the medium and high dose Liangxue Heying Formula groups demonstrated decreased morphological score of the affected limb(P<0.01);increased blood perfusion ratio of the affected side/healthy side(P<0.01);reduced infiltration of thrombus and inflammatory cells in femoral artery and femoral vein tissue,and decreased protein expressions of IL-6 and p-STAT3 in femoral artery tissue(P<0.01).All Liangxue Heying Formula groups shared decreased plasma levels of TNF-α,IL-6,ICAM-1 and VCAM-1(P<0.05,P<0.01);and reduced protein expressions of TNF-�

关 键 词：凉血和营方 血栓闭塞性脉管炎 内皮细胞活化 JAK2/STAT3信号通路 

分 类 号：R285.5[医药卫生—中药学]