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 相对表达水平在用药后均明显增高 （P＜ 0.01） ，STAT3 mRNA 相对表达水平在用药后均明显降低 （P＜0.01） 。结论 中风星蒌通腑胶囊可以增加脑肠肽CCK-8 的表达，调控 IL-10/STAT3 信号通路，从而减轻小鼠脑出血后的继发性炎症反应及细胞毒性脑水肿。

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 reduced on the 3rd and 5th day in the high-dose group （P＜0.01）. The brain water content of mice in the low-dose group was reduced（P＜0.05），and the brain water content of mice in the medium- and high- dose groups was significantly reduced （P＜0.01）. In the low-dose group，the expressions of pro- inflammatory factors TNF-α，IL-6 and JAK-1，STAT3，and p-STAT3 pathway proteins were significantly reduced （P＜0.01），while the expression of IL-1β was reduced（P＜0.05），the expression of IL-10 increased significantly （P＜0.01）. The expression of pro-inflammatory factors TNF-α，IL-1β，IL-6，as well as JAK-1，STAT3，and p-STAT3 pathway proteins in the medium- and high- dose groups was significantly reduced （P＜0.01），the expression of anti-inflammatory factor IL-10 increased significantly（P＜0.01）. The content of CCK-8 in the low- dose group was increased on the 3rd day after treatment（P＜0.05），and the content increased significantly on the 5th day（P＜0.01）. The content of CCK-8 in the medium- and high- dose groups obviously increased on the 3rd and the 5th day after treatment （P＜0.01）. The relative expression level of IL-10 mRNA was significantly increased after treatment（P＜0.01），but the relative expression level of STAT3 mRNA was significantly decreased after treatment （P＜0.01）. Conclusion Zhongfeng Xinglou Tongfu Capsule can target the content of brain-gut peptide CCK-8 and regulate the IL-10/STAT3 signaling pathway to reduce the secondary inflammatory reaction and cytotoxic brain edema after cerebral hemorrhage.

R285.5

“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）