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