氯沙坦降低癫痫大鼠共患抑郁症风险的机制研究  

Study on the mechanism of losartan reducing the risk of comorbid depression in epileptic rats

作　　者：潘楠楠 胡雅纯 廖雪珍 石喆[1] 施海姗[1] PAN Nannan;HU Yachun;LIAO Xuezhen;SHI Zhe;SHI Haishan(The Affiliated Brain Hospital of Guangzhou Medical University,Guangzhou 510370,China)

机构地区：[1]广州医科大学附属脑科医院神经内科,广州510370

出　　处：《中国神经精神疾病杂志》2024年第2期96-101,共6页Chinese Journal of Nervous and Mental Diseases

基　　金：广州市科技计划项目(编号:2023A03J0831);广州市西医类——一般引导项目(编号:20221A010030)。

摘　　要：目的 探讨氯沙坦降低癫痫大鼠共患抑郁症风险的有效性及相关机制。方法 雄性SD大鼠随机分为3组,每组8只:匹罗卡品-氯沙坦(pilocarpine and losartan,PL-L)组接受锂-匹罗卡品腹腔注射建模,后给予氯沙坦干预;匹罗卡品(pilocarpine,PL)组接受锂-匹罗卡品腹腔注射建立癫痫大鼠模型;对照(control,Ctrl)组接受氯化锂腹腔注射。采用体质量增长量和蔗糖偏爱实验对大鼠进行行为学分析,并采用RT-PCR检测大鼠海马区高迁移率族蛋白B1(high-mobility group protein B1,HMGB1)、白介素-1β(interleukin-1β,IL-1β)、白介素-6(interleukin-6,IL-6)mRNA的相对表达量。结果 PL组大鼠与Ctrl组相比,出现体质量增长量[(12.68±5.23)g vs.(41.08±15.87)g,P<0.01]和糖水偏爱率(53.85%±10.14%vs. 88.56%±16.53%, P<0.01)下降,大鼠海马区HMGB1 mRNA相对表达量增加(4.17±1.23 vs. 1.00±0.02, P<0.01),同时IL-1β(4.95±1.67 vs. 1.02±0.27, P<0.01)、IL-6(2.75±1.20 vs. 1.01±0.19, P<0.05)mRNA相对表达量也增加;PL-L组大鼠与PL组相比,体质量增长量[(37.97±10.24)g vs.(12.68±5.23)g, P<0.01]和糖水偏爱率(77.50%±7.35%vs. 53.85%±10.14%, P<0.05)增加,海马区HMGB1 mRNA相对表达量下降(0.76±0.27 vs. 4.17±1.23, P <0.01),同时IL-1β(0.67±0.21 vs. 4.95±1.67, P<0.01)、IL-6(0.95±0.27 vs. 2.75±1.20, P<0.05)mRNA相对表达量也下降。结论 氯沙坦可以减少癫痫大鼠共患抑郁症的发生,其可能的机制是氯沙坦减少HMGB1释放,从而减轻大鼠海马区炎症因子(IL-1β、IL-6)的表达,降低癫痫共患抑郁症的风险。Objective To investigate the effectiveness and mechanisms of losartan in improving comorbid depression in epileptic rats.Methods Male rats were randomly divided into three groups:The losartan-pilocarpine group(PL-L)received intraperitoneal injection of lithium-pilocarpine to establish the epilepsy model,and then followed by losartan intervention.The pilocarpine group(PL)received intraperitoneal injection of lithium-pilocarpine to establish the epilepsy model.The control group(Ctrl)received intraperitoneal injection of lithium chloride.We used the body weight gain and sucrose preference test to analyze the behavior of rats in each group,and RT-PCR was used to examine the expression of High mobility group protein B1(HMGB1)、interleukin-1β(IL-1β)and interleukin-6(IL-6)mRNA in hippocampus of rats in each group.Results Compared to the Ctrl group,rats in the PL group showed significantly decreased body weight gain[(12.68±5.23)g vs.(41.08±15.87)g,P<0.01]and sucrose preference rate(53.85%±10.14%)vs.(88.56%±16.53%,P<0.01).The expression of HMGB1 mRNA(4.17±1.23 vs.1.00±0.02,P<0.01)was significantly increased.The expression of IL-1β(4.95±1.67 vs.1.02±0.27,P<0.01)and IL-6(2.75±1.20 vs.1.01±0.19,P<0.05)were significantly increased too.Compared with the PL group,rats in the PL group showed significantly increased body weight gain[(37.97±10.24)g vs.(12.68±5.23)g,P<0.01]and sucrose preference rate(77.50%±7.35%vs.53.85%±10.14%,P<0.05).The expression of HMGB1(0.76±0.27 vs.4.17±1.23,P<0.01)was significantly decreased.The expression of IL-1β(0.67±0.21 vs.4.95±1.67,P<0.01)and IL-6(0.95±0.27 vs.2.75±1.20,P<0.05)mRNA were significantly decreased too.Conclusion Losartan can reduce the incidence of comorbid depression in epileptic rats,The possible mechanism is that losartan reduces HMGB1 release,so as to reduce the inflammatory factors(IL-1β,IL-6)in the hippocampus of rats.It can reduce the incidence of depression like behavior disorder in rats with epilepsy.

关 键 词：氯沙坦 高迁移率族蛋白B1 炎症因子 白介素-1Β 白介素-6 癫痫 抑郁症 

分 类 号：R724.1[医药卫生—儿科]