| 王宝祥,许俊杰.人参皂苷Rd通过SHH信号通路促进MCAO模型大鼠血管新生机制研究[J].浙江中西医结合杂志,2023,33(4): |
| 人参皂苷Rd通过SHH信号通路促进MCAO模型大鼠血管新生机制研究 |
| The study of ginsenoside Rd promotes angiogenesis through SHH signaling pathway in MCAO model rats |
| 投稿时间：2022-05-28 修订日期：2023-03-01 |
| DOI： |
| 中文关键词: 大鼠 人参皂苷 脑梗死 中动脉闭塞模型 声波刺猬信号 |
| 英文关键词:Rat Ginsenosides, Stroke, MCAO, SHH |
| 基金项目:浙江省医药卫生科技计划项目(编号:2020RC123) |
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| 中文摘要: |
| 摘 要 目的 探讨人参皂苷Rd对大脑中动脉闭塞（MCAO）模型大鼠血管新生的影响及相关机制。方法 40只SD大鼠随机数字表法分为假手术组、模型组、人参皂苷Rd组（Rd组）、人参皂苷Rd+环靶明（CYC）组（Rd+CYC组），每组10只。采用线栓塞法建立MCAO模型大鼠，假手术组仅分离左侧颈总动脉、颈外动脉和颈内动脉。造模成功后，Rd组大鼠按照50 mg/kg给予人参皂苷Rd，Rd+CYC组按50 μg/kg给予CYC腹腔注射，假手术组和模型组给予同等剂量的生理盐水。每天给药1次，连续给药2周。各组大鼠神经功能评分，TTC方法检测脑梗死体积，显微镜下观察脑组织毛细血管密度，蛋白质免疫印记检测血管生成相关分子和声波刺猬信号蛋白（SHH）、血管内皮生长因子（VEGF）、血管紧张素-1（ANG-1）、血管紧张素-2（ANG-2）蛋白表达水平。结果 与模型组比较，Rd组大鼠神经功能评分显著降低[（1.000±0.471）分比（3.100±0.738）分，P＜0.01]；脑梗死体积显著减少[（18.120±3.735）%比（33.920±2.954）%，P＜0.01]；脑梗死区域毛细血管数量显著增加[（389.60±23.34）条比（54.37±11.21）条，P＜0.01]；血管生成相关分子SHH、VEGF、ANG-1、ANG-2蛋白表达水平显著升高[SHH：（1.267±0.038）比（0.533±0.043）；VEGF：（0.866±0.035）比（0.596±0.055）；ANG-1：（0.880±0.036）比（0.510±0.056）；ANG-2：（0.870±0.040）比（0.386±0.045），P均＜0.01]。与Rd组比较，Rd+CYC组大鼠神经功能评分显著升高[（2.700±0.675）分比（1.000±0.471）分，P＜0.01]；脑梗死体积显著增加[（28.910±4.491）%比（18.120±3.735）%，P＜0.01]；脑梗死区域毛细血管数量显著减少[（180.90±37.37）条比（389.60±23.34）条，P＜0.01]；血管生成相关分子VEGF、ANG-1、ANG-2蛋白表达水平显著下降[VEGF：（0.600±0.007）比（0.866±0.035）；ANG-1：（0.570±0.027）比（0.880±0.036）；ANG-2：（0.476±0.038）比（0.87±0.04），P均＜0.01]。结论 人参皂苷Rd可能通过SHH信号通路促进脑梗死区域血管生成，改善MCAO模型大鼠预后并发挥保护作用。
关键词 大鼠；人参皂苷；脑梗死；大脑中动脉闭塞；声波刺猬信号蛋白 |
| 英文摘要: |
| ABSTRACT Objective To investigate the effect and related mechanism of ginsenoside Rd in middle cerebral artery occlusion (MCAO) model rats. Methods The MCAO model of SD rats was established by thread embolization, and 40 rats were randomly divided into 4 groups: sham operation group , MCAO model group , ginsenoside Rd group (Rd group), ginseng Saponin Rd combined with Cyclopamine(CYC) group (Rd + CYC group), 10 rats in each group. The neurological function scores of the rats in each group, the volume of cerebral infarction (CI) was detected by TTC method, the capillary density of brain tissue was observed under a microscope, and the angiogenesis-related molecules, sonic hedgehog (SHH) and vascular endothelial growth were detected by western blotting (WB). The protein expression levels of factor (VEGF), angiotensin-1 (ANG-1), and angiotensin-2 (ANG-2). Results The neurological function score of the Rd group (1.000±0.471) was significantly lower than that of the MCAO modeln group(3.100±0.738) (P<0.01); the CI volume of the Rd group (18.120±3.735) was significantly lower than that of the MCAO model group (33.920±2.954), significantly decreased (P<0.01); the number of capillaries in the CI area in the Rd group (389.60±23.34) was significantly higher than that in the MCAO model group(54.37±11.21) (P<0.01); the ginsenoside Rd group , compared with the MCAO model group, the protein expression levels of angiogenesis-related molecules SHH, VEGF, ANG-1, and ANG-2 were significantly increased [SHH：（1.267±0.038）vs（0.533±0.043）；VEGF：（0.866±0.035）vs（0.596±0.055）；ANG-1：（0.88±0.036）vs（0.51±0.056）；ANG-2：（0.87±0.04）vs（0.386±0.045），all P＜0.01]. The SHH inhibitor CYC weakened the protective effect and angiogenesis effect of ginsenoside Rd, and decreased the expression levels of VEGF, ANG-1, and ANG-2. Conclusion Ginsenoside Rd promotes angiogenesis in the CI region through SHH signaling pathway, improves the prognosis of MCAO model rats and exerts a protective effect.
KEY WORDS Rat；Ginsenosides；Stroke；MCAO；SHH |
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