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 天的逃避潜伏期明显缩短（P＜0.05），钩藤降压 解郁方高、低剂量组大鼠第4 天的逃避潜伏期明显缩短（P＜0.05）。钩藤降压解郁方高、中、低剂量组大鼠第 1 次穿越平台区时间显著缩短（P＜0.01），钩藤降压解郁方中、低剂量组大鼠穿越平台区次数明显增加（P＜ 0.05），平台区滞留时间明显延长（P＜0.05）。给药组海马神经元损伤程度减轻，细胞核皱缩情况明显改善，自 噬小体减少。钩藤降压解郁方高、中剂量组大鼠海马组织中促炎因子IL-1β、IL-18 含量显著降低（P＜0.05， P＜0.01），钩藤降压解郁方高剂量组大鼠海马组织中抗炎因子IL-10 含量显著升高（P＜0.01）。钩藤降压解郁 方高、中、低剂量组海马组织中的LC3Ⅱ/LC3Ⅰ蛋白表达比值显著下调（P＜0.01），Bcl-2 蛋白表达显著上调 （P＜0.01）；钩藤降压解郁方高、中剂量组大鼠海马组织中Beclin1 蛋白表达明显下调（P＜0.05，P＜0.01）。 结论 钩藤降压解郁方可降低HD 大鼠尾动脉压，改善其学习记忆能力，缓解海马神经元损伤，其机制可能与 减少促炎因子释放，提高抗炎因子水平，调控海马自噬相关蛋白LC3Ⅱ/LC3Ⅰ、Beclin1 和Bcl-2 的表达有关。

Abstract: 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 LC3Ⅰ and LC3Ⅱ in 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 nucleus was shrunk， and a large number of autophagosomes appeared； the contents of IL-1β and IL-18 in hippocampus were significantly increased （P＜0.01）. The ratio of LC3 Ⅱ/LC3 Ⅰ protein expression and the expression of Beclin1 protein in hippocampus were significantly up-regulated （P＜0.05， P＜0.01）， and the expression of Bcl-2 protein was significantly down-regulated （P＜0.01）. Compared with the model group，the SBP of rats in the low-dose group of Gouteng Jiangya Jieyu Prescription was significantly decreased at the weeks 1，3， 4，5，6 （P＜0.01），and the DBP was significantly decreased at weeks 1，3，4，5 （P＜0.05，P＜0.01）. The SBP of the rats in the medium-dose group of Gouteng Jiangya Jieyu Prescription was significantly decreased at weeks 1，5，6（P＜0.01），and the DBP was significantly decreased at week 4（P＜0.05） . The SBP of rats in the highdose group of Gouteng Jiangya Jieyu Prescription was significantly decreased in the first week （P＜0.01） . The escape latency of rats in the high- and medium- dose groups of Gouteng Jiangya Jieyu Prescription was significantly shortened on the third day （P＜0.05），and the escape latency of rats in the high- and low- dose groups of Gouteng Jiangya Jieyu Prescription was significantly shortened on the fourth day （P＜0.05）. The first crossing platform time of rats in the high- ， medium- and low- dose groups of Gouteng Jiangya Jieyu Prescription was significantly shortened （P＜0.01）. The times of rats crossing the platform area in the medium- and low- dose groups of Gouteng Jiangya Jieyu Prescription were significantly increased （P＜0.05），and the retention time in the platform area was significantly prolonged （P＜0.05）. In the administration group， the degree of hippocampal neuron damage was reduced，the nuclear shrinkage was significantly improved，and the autophagosomes were reduced. The contents of pro-inflammatory factors IL-1β and IL-18 in the hippocampus of rats in the high- and medium- dose groups of Gouteng Jiangya Jieyu Prescription were significantly decreased （P＜0.05， P＜0.01）. The content of antiinflammatory factor IL-10 in the hippocampus of rats in the high-dose group of Gouteng Jiangya Jieyu Prescription was significantly increased （P＜0.01）. The protein expression ratio of LC3Ⅱ/LC3Ⅰ in hippocampus of high- ， medium- and low- dose groups of Gouteng Jiangya Jieyu Prescription was significantly down-regulated （P＜0.01）， and the expression of Bcl-2 protein was significantly up-regulated （P＜0.01）. The expression of Beclin1 protein in the hippocampus of the high- and medium- dose groups of Gouteng Jiangya Jieyu Prescription was significantly down-regulated （P＜0.05， P＜0.01）. Conclusion Gouteng Jiangya Jieyu Prescription can reduce the tail arterial pressure of HD rats， improve their learning and memory ability， and alleviate hippocampal neuronal damage. The mechanism may be related to reducing the release of inflammatory factors，increasing the level of anti-inflammatory factors，and regulating the expression of hippocampal autophagy-related proteins LC3Ⅱ/LC3Ⅰ，Beclin1 and Bcl-2.

R285.5

湖南省自然科学基金项目（2021JJ80065）；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）；湖南省中医药科研项目（A2023019）；湖南省卫生健康委员会科研计划项目（C202313056551，D202313057728）。