滋水清肝饮通过抑制细胞焦亡减轻抑郁模型大鼠海马区炎症  

Zishui Qinggan Decoction Alleviates Hippocampal Inflammation in a Rat Model of Depression by Inhibiting Pyroptosis

作　　者：杨峰 朱雯[1] 张雯 李祥婷 向军[1,2] 范越 蔡定芳[1,2] YANG Feng;ZHU Wen;ZHANG Wen;LI Xiangting;XIANG Jun;FAN Yue;CAI Dingfang(Department of Integrated Traditional Chinese and Western Medicine,Zhongshan Hospital,Fudan University,Shanghai 200030,China;Institute of Integrated Traditional Chinese and Western Medicine on Neurology,Fudan University,Shanghai 200030,China)

机构地区：[1]复旦大学附属中山医院中西医结合科,上海200030 [2]复旦大学中西医结合神经病学研究所,上海200030

出　　处：《安徽中医药大学学报》2023年第2期85-90,共6页Journal of Anhui University of Chinese Medicine

基　　金：国家自然科学基金项目(8190140530);复旦大学附属中山医院青年基金项目(2021ZSQN21)。

摘　　要：目的探讨滋水清肝饮对抑郁模型大鼠海马区细胞焦亡的作用及其机制。方法将60只SD大鼠留取12只作为正常对照组,其余大鼠采用慢性不可预见性温和应激(chronic unpredicted mild stress,CUMS)复制抑郁模型。将模型复制成功的48只大鼠随机分为模型组,滋水清肝饮低、中、高剂量组,每组12只。滋水清肝饮低、中、高剂量组分别给予滋水清肝饮12、24、48 g/kg,模型组和对照组分别给予等容积的生理盐水。采用强迫游泳实验和糖水偏好实验评价大鼠抑郁样行为的改变。采用Western blot法检测大鼠海马区焦亡相关蛋白GSDMD、Caspase-1蛋白表达水平;RT-qPCR法检测GSDMD、Caspase-1 mRNA的表达水平;ELISA法检测大鼠海马匀浆中白细胞介素(interleukin,IL)-1β、IL-18及乳酸脱氢酶(lactate dehydrogenase,LDH)水平;免疫荧光法观察大鼠海马区GSDMD蛋白表达水平。结果与对照组比较,模型组大鼠在强迫游泳实验中的潜伏期显著缩短(P<0.05),静止不动时间显著增加(P<0.05),在糖水偏好实验中糖水消耗显著减少(P<0.05);模型组大鼠海马区焦亡蛋白GSDMD和Caspase-1蛋白及mRNA表达水平显著升高(P<0.05),IL-1β、IL-18、LDH表达水平显著升高(P<0.05)。与模型组比较,滋水清肝饮低、中、高剂量组大鼠在强迫游泳实验中潜伏期显著增加(P<0.05),静止不动时间显著降低(P<0.05);在糖水偏好实验中糖水消耗显著增加(P<0.05);大鼠海马区焦亡蛋白Caspase-1和GSDMD蛋白及mRNA表达水平显著降低(P<0.05),IL-1β、IL-18、LDH表达水平显著降低(P<0.05)。结论滋水清肝饮可通过抑制细胞焦亡减轻CUMS模型大鼠海马区炎症。Objective To investigate the effect of Zishui Qinggan Decoction on hippocampal pyroptosis and its mechanism in a rat model of depression.Methods A total of 60 Sprague-Dawley rats were selected,among which 12 were established as normal control group and the other 48 rats were used to establish a model of depression by chronic unpredicted mild stress(CUMS).After successful modeling,the 48 rats were randomly divided into model group and low-,middle-,and high-dose Zishui Qinggan Decoction groups,with 12 rats in each group.The rats in the low-,middle-,and high-dose Zishui Qinggan Decoction groups were given Zishui Qinggan Decoction at doses of 12,24,and 48 g/kg,respectively,and those in the model group and the control group were given an equal volume of normal saline.The forced swimming test and the sucrose preference test were used to evaluate the change in depression-like behavior in rats.Western blot was used to measure the expression levels of the pyroptosis-related proteins GSDMD and Caspase-1 in the hippocampus,and RT-qPCR was used to measure the mRNA expression levels of GSDMD and Caspase-1;ELISA was used to measure the levels of interleukin-1β(IL-1β),interleukin-18(IL-18),and lactate dehydrogenase(LDH)in hippocampus homogenate;immunofluorescence assay was used to measure the expression level of GSDMD in the hippocampus.Results Compared with the control group,the model group had a significant reduction in latency period(P<0.05)and a significant increase in immobility time(P<0.05)in the forced swimming test,as well as a significant reduction in sugar water consumption in the sucrose preference test,and the model group also had significant increases in the protein and mRNA expression levels of the pyroptosis-related proteins GSDMD and Caspase-1 in the hippocampus(P<0.05)and the expression levels of IL-1β,IL-18,and LDH(P<0.05).Compared with the model group,the low-,middle-,and high-dose Zishui Qinggan Decoction groups had a significant increase in latency period(P<0.05)and a significant reduction in immobility

关 键 词：滋水清肝饮 抑郁症 细胞焦亡 炎症 

分 类 号：R285.5[医药卫生—中药学]