钩藤降压解郁方对高血压并发抑郁症大鼠学习记忆能力及海马自噬相关蛋白表达的影响  

Effects of Gouteng Jiangya Jieyu Prescription on Learning and Memory Ability and Hippocampal Autophagy-Related Protein Expression in Rats with Hypertension Complicated with Depression

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作  者:赵红霞 刘叶倩 陈蕾 黄铃格 李弘 马丹凤[4] 陈春茗 曾水清 任卫琼[1] ZHAO Hongxia;LIU Yeqian;CHEN Lei;HUANG Lingge;LI Hong;MA Danfeng;CHEN Chunming;ZENG Shuiqing;REN Weiqiong(The First Affiliated Hospital of Hunan University of Chinese Medicine,Changsha 410007 Hunan,China;Chongqing Wanzhou Institue for Food and Drug Control,Wanzhou 404000 Chongqing,China;The Second People’s Hospital of Anhui Province,Hefei 230041 Anhui,China;Hunan Children’s Hospital,Changsha 410007 Hunan,China)

机构地区:[1]湖南中医药大学第一附属医院,湖南长沙410007 [2]重庆市万州食品药品检验所,重庆万州404000 [3]安徽省第二人民医院,安徽合肥230041 [4]湖南省儿童医院,湖南长沙410007

出  处:《中药新药与临床药理》2024年第5期646-655,共10页Traditional Chinese Drug Research and Clinical Pharmacology

基  金:湖南省自然科学基金项目(2021JJ80065);湖南省中医药科研项目(A2023019);湖南省中药粉体与创新药物研究省部共建国家重点实验室培育基地开放基金项目(21PTKF1010);湖南省卫生健康委员会科研计划项目(C202313056551,D202313057728)。

摘  要:目的研究钩藤降压解郁方(钩藤、天麻、地龙、葛根、丹参等)对高血压并发抑郁症(Hypertension complicated with depression,HD)大鼠学习记忆能力、海马炎症反应和自噬相关蛋白表达的影响。方法将30只自发性高血压大鼠(SHR)随机分为模型组、阳性对照组(苯磺酸左旋氨氯地平0.45 mg·kg^(-1)+盐酸氟西汀1.80 mg·kg^(-1))及钩藤降压解郁方高、中、低剂量组(25.38、12.69、6.34 g·kg^(-1)),另取6只SD大鼠作空白对照组。采用慢性温和不可预见性应激联合孤养的方法干预SHR大鼠,复制HD大鼠模型。造模同时灌胃给药,每天1次,连续6周。采用无创血压计测量大鼠尾动脉收缩压(SBP)和舒张压(DBP);通过Morris水迷宫实验检测大鼠学习记忆能力;透射电镜观察大鼠海马神经元超微结构;ELISA法检测海马组织中白细胞介素1β(IL-1β)、IL-18及IL-10含量;免疫组化法检测海马组织中自噬相关蛋白Beclin1、Bcl-2的表达;Western Blot法检测海马组织中自噬相关蛋白LC3Ⅰ、LC3Ⅱ的表达。结果与空白对照组比较,模型组大鼠第1~6周的SBP、DBP均显著升高(P<0.01);第3、4天的逃避潜伏期显著延长(P<0.01);第1次穿越平台区时间显著延长(P<0.01),穿越平台区次数明显减少(P<0.05),平台区滞留时间显著缩短(P<0.01);海马神经元胞体明显肿胀,嵴破坏,细胞核皱缩,出现大量自噬小体;海马组织中IL-1β、IL-18含量显著增加(P<0.01);海马组织中LC3Ⅱ/LC3Ⅰ蛋白表达比值和Beclin1蛋白表达明显上调(P<0.05,P<0.01),Bcl-2蛋白表达显著下调(P<0.01)。与模型组比较,钩藤降压解郁方低剂量组大鼠第1、3、4、5、6周的SBP显著降低(P<0.01),第1、3、4、5周的DBP明显降低(P<0.05,P<0.01);钩藤降压解郁方中剂量组大鼠第1、5、6周的SBP显著降低(P<0.01),第4周的DBP明显降低(P<0.05);钩藤降压解郁方高剂量组大鼠第1周的SBP显著降低(P<0.01)。钩藤降压解郁方高、中剂量组大鼠第3天的逃�Objective To study the effects of Gouteng Jiangya Jieyu Prescription(Uncariae Ramulus cum Uncis,Gastrodiae Rhizoma,Pheretima,Puerariae Lobatae Radix,Salviae Miltiorrhizae Radix et Rhizoma,etc.)on learning and memory ability,hippocampal inflammatory response and autophagy-related protein expression in rats with hypertension complicated with depression(HD).Methods Thirty spontaneously hypertensive rats(SHR)were randomly divided into model group,positive control group(Levamlodipine Besylate 0.45 mg·kg^(-1)+Fluoxetine Hydrochloride 1.80 mg·kg^(-1))and Gouteng Jiangya Jieyu Prescription high-,medium-and low-dose groups(25.38,12.69,6.34 g·kg^(-1)).Another 6 SD rats were used as blank control group.The SHR rats were intervened by chronic mild unpredictable stress combined with solitary rearing to replicate the HD rat model.At the same time,intragastric administration was given once a day for 6 weeks.The systolic blood pressure and diastolic blood pressure of rat tail artery were measured by non-invasive sphygmomanometer.The learning and memory ability of rats was detected by Morris water maze test.The ultrastructure of hippocampal neurons was observed by transmission electron microscope.The contents of interleukin-1β(IL-1β),IL-18 and IL-10 in hippocampus were detected by ELISA.The expression of autophagy-related proteins Beclin1 and Bcl-2 in hippocampus was detected by immunohistochemistry.The expression of autophagy-related proteins LC3Ⅰand LC3Ⅱin hippocampus was detected by Western Blot.Results Compared with the blank control group,the SBP and DBP of the rats in the model group were significantly increased from week 1-6(P<0.01).The escape latency was significantly prolonged on the third and fourth day(P<0.01).The first time of crossing the platform was significantly prolonged(P<0.01),the times of crossing the platform area was significantly reduced(P<0.05),and the retention time of the platform area was significantly shortened(P<0.01).The neuronal cell body was obviously swollen,the ridge was destroyed,the nu

关 键 词:钩藤降压解郁方 高血压并发抑郁症 自噬蛋白 炎症因子 学习记忆能力 海马神经元损伤 大鼠 

分 类 号:R285.5[医药卫生—中药学]

 

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