滋肾泻青汤对ADHD模型大鼠前额叶多巴胺受体脱敏-复敏信号通路的影响  

Effects of Zishen Xieqing Tang on Dopamine Signaling Pathway of Desensitization/Resensitization in Attention Deficit Hyperactivity Disorder Rats'Prefrontal Cortex

作　　者：孙继超 张碧霞 李伟伟[1] SUN Ji-chao;ZHANG Bi-xia;LI Wei-wei(The First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530023,China)

机构地区：[1]广西中医药大学第一附属医院,广西南宁530023

出　　处：《南京中医药大学学报》2022年第12期1137-1142,共6页Journal of Nanjing University of Traditional Chinese Medicine

基　　金：国家自然科学基金青年科学基金项目(81804146);国家自然科学基金地区科学基金项目(82260953);广西自然科学基金青年基金项目(2017JJB140344y);广西自然科学基金面上项目(2020JJA140275);广西高校中青年教师基础能力提升项目(2018KY0281);广西中医药大学引进博士科研启动基金项目(2017BS046)。

摘　　要：目的探讨中药方滋肾泻青汤对注意缺陷多动障碍模型大鼠(Spontaneously hypertensive rat,SHR)行为学表现及前额叶多巴胺受体脱敏-复敏信号通路的影响。方法50只SHR大鼠随机分为模型组、利他林组(2 mg·kg^(-1))、滋肾泻青汤低剂量组、中剂量组、高剂量组(6.0、12.1、24.1 g·kg^(-1)),每组10只,另设Wistar京都大鼠(Wistar Kyoto rat,WKY)为正常对照组。每日灌胃2次,在此期间进行相应的行为学检测,治疗4周后取大鼠前额叶组织。分别用Western blot及qPCR检测各组大鼠前额叶组织中GRK-6、β-arrestin2、NCS-1、PP2A及PSD-95等蛋白和mRNA表达水平。结果利他林及滋肾泻青汤能改善SHR大鼠的行为学表现。与正常组相比,模型组大鼠前额叶中β-arrestin2、NCS-1、PP2A、PSD-95蛋白和mRNA表达水平有下调趋势或显著下调(P<0.05),而GRK-6的表达水平上调(P<0.05);经治疗后,与模型组相比,利他林组、滋肾泻青汤各剂量组前额叶中β-arrestin2、NCS-1、PSD-95、PP2A蛋白和mRNA表达水平有上调趋势或明显上调(P<0.05),而GRK-6的表达水平明显降低(P<0.05)。结论利他林及滋肾泻青汤能增加模型大鼠前额叶多巴胺受体的活性,多巴胺受体脱敏-复敏信号通路可能是滋肾泻青汤治疗ADHD的潜在途径之一。OBJECTIVE To investigate the effects of Zishen Xieqing Tang(ZXT)on attention deficit hyperactivity disorder(ADHD)related behavior and dopamine signaling pathway of desensitization and resensitization in spontaneously hypertensive rats’prefrontal cortex.METHODS 10 Wistar Kyoto rats were set as normal control group.50 SHR rats were randomly divided into 5 groups including model group,methylphenidate(MPH)group(2 mg·kg^(-1)by gavage),and high,middle,low dose of ZXT groups(ig ZXT with the crude drug dosage 6.0,12.1,24.1 g·kg^(-1)respectively).Rats were orally given the drugs twice a day,then,behavior experiment was done to test the ADHD related behavior changes.After 4 weeks of treatment,the prefrontal cortex of rats were collected for further study.Real-time PCR and Western blot were used to test the protein or mRNA expression of GRK-6,β-arrestin2,NCS-1,PP2A and PSD-95 in SHR rats’prefrontal cortex.RESULTS MPH group and ZXT groups could improve the ADHD related behavioral performance of SHR.Statistic difference ofβ-arrestin2,GRK-6,NCS-1,PSD-95,PP2A and PKA expression were observed among different groups(P<0.05).Comparing with normal control group,theβ-arrestin2,NCS-1,PSD-95 and PP2A expression of SHR rats’prefrontal cortex in model group were much lower(P<0.05).After treatment with ZXT,comparing the model group,the expression ofβ-arrestin2,NCS-1,PSD-95 and PP2A in MPH group and every-dosage group of ZXT were much higher in both parts(P<0.05).At the meanwhile,the expression of GRK-6 was observed on the contrary behavior.CONCLUSION Both MPH and Zishen Xieqing Tang can affect the function of dopamine receptors by regulating desensitization and re-sensitization,thus improve the ADHD related symptom.

关 键 词：滋肾泻青汤 注意缺陷多动障碍 多巴胺受体 脱敏-复敏 中医药 

分 类 号：R285.5[医药卫生—中药学]