中风星蒌通腑胶囊介导CCK-8调控IL-10/STAT3信号通路改善脑出血小鼠的炎症损伤  

Zhongfeng Xinglou Tongfu Capsule Improves Inflammatory Damage in Mice with Cerebral Hemorrhage by Mediating CCK-8 to Regulate the IL-10/STAT3 Signaling Pathway

作　　者：王思媛 张燕平[2] 严美茹 武雨幸 李祎 岳晓晴 王新志[2] 刘向哲[2] WANG Siyuan;ZHANG Yanping;YAN Meiru;WU Yuxing;LI Yi;YUE Xiaoqing;WANG Xinzhi;LIU Xiangzhe(The First School of Clinical Medicine,Henan University of Traditional Chinese Medicine,Zhengzhou 450000 Henan,China;Encephalopathy Hospital,the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450000 Henan,China;Chengcheng County Hospital,Weinan 715200 Shanxi,China)

机构地区：[1]河南中医药大学第一临床医学院,河南郑州450000 [2]河南中医药大学第一附属医院脑病医院,河南郑州450000 [3]澄城县医院,陕西渭南715200

出　　处：《中药新药与临床药理》2024年第6期832-840,共9页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：“十四五”国家重点研发计划“中医药现代化研究”重点专项(2022YFC3501103);河南省中医药管理局基金资助项目(2022ZY1009);河南省高等学校重点科研基金资助项目(22A320037);河南省中医药管理局基金资助项目(2024ZY1007)。

摘　　要：目的探讨中风星蒌通腑胶囊介导胆囊收缩素八肽(CCK-8)对白细胞介素10(IL-10)/信号转导与转录激活子3(STAT3)信号通路对脑出血小鼠的脑部炎症反应的调控作用及机制。方法将110只C57BL/6小鼠按随机数字表法分为假手术组、脑出血组及中风星蒌通腑胶囊低、中、高剂量组,每组22只。采用胶原酶法建立脑出血模型,模型复制2 h后进行中风星蒌通腑胶囊混悬液灌胃(10 mL·kg^(-1)),假手术组与脑出血组灌以等量的生理盐水。记录小鼠的神经功能学评分及左转率;于术后72 h采用干湿质量法检测脑含水量;于术后72 h采用Western Blot法检测小鼠血肿周围肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、白细胞介素10(IL-10)以及Janus激酶1(JAK-1)、STAT3、磷酸化STAT3(p-STAT3)通路蛋白的相对表达水平;于术后第3、5天采用Elisa法检测小鼠CCK-8的相对表达水平;采用荧光定量PCR(qPCR)法检测IL-10、STAT3的mRNA的表达水平。结果与脑出血组比较,中风星蒌通腑胶囊低、中、高剂量组干预治疗后,第3天及第5天小鼠改良神经功能缺陷(NDS)评分明显降低(P<0.01),低剂量组第3天及第5天左转率降低(P<0.05),中剂量组第3天(P<0.05)及第5天(P<0.01)左转率降低,高剂量组第3天及第5天左转率明显降低(P<0.01)。低剂量组小鼠脑含水量减少(P<0.05),中、高剂量组小鼠脑含水量明显减少(P<0.01)。低剂量组促炎因子TNF-α、IL-6及JAK-1、STAT3、p-STAT3通路蛋白的表达均明显减少(P<0.01),IL-1β表达减少(P<0.05),抑炎因子IL-10表达明显增加(P<0.01);中、高剂量组促炎因子TNF-α、IL-1β、IL-6及JAK-1、STAT3、p-STAT3通路蛋白的表达均明显减少(P<0.01),抑炎因子IL-10表达明显增加(P<0.01)。低剂量组CCK-8的含量在用药后第3天增加(P<0.05),第5天含量明显增加(P<0.01);中、高剂量组CCK-8的含量在用药后第3天及第5天明显增加(P<0.01)。IL-10的mRNA相对表达Objective To explore the regulatory effect and mechanism of Zhongfeng Xinglou Tongfu Capsule on the brain inflammatory response of mice with cerebral hemorrhage through cholecystokinin octapeptide(CCK-8)mediated the interleukin 10(IL-10)/signal transduction and transcriptional activator 3(STAT3)signaling pathway.Methods A total of 110 C57BL/6 mice were divided into sham operation group,cerebral hemorrhage group,Zhongfeng Xinglou Tongfu Capsule low-,medium-,and high-dose groups according to the random number table method,with 22 mice in each group.The intracerebral hemorrhage model was established by collagenase method.At 2 hours after the establishment of the model,Zhongfeng Xinglou Tongfu Capsule suspension was intragastrically administered at a dose of 10 mL·kg^(-1).The sham operation group and the cerebral hemorrhage group were intragastrically administered with the same dose of normal saline.The neurofunctional score and left-turn rate of the mice were recorded.The dry and wet weight method was used to detect brain water content on the 72 h after surgery,and the Western Blot method was used to detect tumor necrosis factor-α(TNF-α),interleukin 1β(IL-1β),interleukin 6(IL-6),interleukin 10(IL-10),and the relative expression levels of JAK-1,STAT3,and p-STAT3 pathway proteins around the hematoma of mice at 72 h after surgery.On the 3rd and 5th day after surgery,Elisa method was used to detect the relative expression level of CCK-8,qPCR method was used to detect the expression levels of IL-10 and STAT3 mRNA.Results Compared with the cerebral hemorrhage group,the NDS scores of mice in the low-,medium-,and high-dose groups of Zhongfeng Xinglou Tongfu Capsules were significantly reduced on the 3rd and 5th days after intervention treatment(P<0.01).And the left-turn rate in the low-dose group on the 3rd and 5th days after intervention treatment was reduced(P<0.05),the left-turn rate in the medium-dose group was reduced on the 3rd day(P<0.05)and the 5th day(P<0.01).Furthermore,the left-turn rate was obviously reduce

关 键 词：脑出血 中风星蒌通腑胶囊 通腑法 胆囊收缩素八肽(CCK-8) IL-10 STAT3 炎症 小鼠 

分 类 号：R285.5[医药卫生—中药学]