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Z-没药甾酮联合11-羰基-β-乙酰乳香酸对脑缺血再灌注损伤模型大鼠的改善作用研究
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| 篇名： | Z-没药甾酮联合11-羰基-β-乙酰乳香酸对脑缺血再灌注损伤模型大鼠的改善作用研究 |
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| 摘要： | 目的：研究Z-没药甾酮（Z-GL）联合11-羰基-β-乙酰乳香酸（AKBA）对脑缺血再灌注损伤模型大鼠的改善作用。方法：将雄性SD大鼠随机分为假手术组、模型组和Z-GL+AKBA低、高剂量组（二者低、高剂量均分别为25、50 mg/kg），每组10只。除假手术组外，其余各组均采用线栓法复制大脑中动脉闭塞/再灌注损伤模型。各给药组大鼠均于再灌注后灌胃相应药物，假手术组和模型组大鼠灌胃等容二甲基亚砜，每12 h给药1次，连续7 d。采用改良Longa评分法评价各组大鼠的神经功能缺损情况，采用苏木精-伊红染色法观察各组大鼠脑组织的病理学变化，采用TTC法检测其脑梗死面积并计算脑梗死百分比，采用TUNEL法检测其脑组织中在体细胞凋亡情况，采用免疫荧光染色法、免疫印迹法分别检测其脑组织中CD34、血管内皮生长因子（VEGF）、Delta样配体4（DLL4）的表达情况。结果：与假手术组比较，模型组大鼠脑组织皮层细胞数量减少且排列不规则，可见明显梗死区，并伴有新生血管明显减少；其神经功能缺损评分和脑梗死面积百分比均显著升高，TUNEL阳性细胞数显著增多，CD34、VEGF、DLL4的表达水平均显著降低（P＜0.05或P＜0.01）。与模型组比较，各给药组大鼠上述症状均有明显改善，其神经功能缺损评分和脑梗死面积百分比均显著降低，TUNEL阳性细胞数显著减少，CD34、VEGF、DLL4的表达水平均显著升高，且Z-GL+AKBA高剂量组神经功能缺损评分、脑梗死面积百分比、TUNEL阳性细胞数均显著低于或少于低剂量组，CD34、DLL4的表达水平均显著高于低剂量组（P＜0.05或P＜0.01）。结论：Z-GL和AKBA联用可减轻脑缺血再灌注损伤模型大鼠的神经功能缺损，改善其脑损伤；这种作用可能与促进血管新生以及上调VEGF、DLL4蛋白的表达有关，并具有一定的剂量依赖性。 |
| ABSTRACT： | OBJECTIVE： To study the improvement effects of Z-guggulsterone （Z-GL） combined with acetyl-11-keto-β- boswellic acid （AKBA） on cerebral ischemia-reperfusion injury model rats. METHODS： Male SD rats were randomly divided into sham operation group， model group， Z-GL+AKBA low-dose and high-dose groups （25， 50 mg/kg）， with 10 rats in each group. Except for sham operation group， middle cerebral artery occlusion/reperfusion injury model was induced by suture method in other groups. Administration groups were given relevant medicine intragastrically after reperfusion； sham operation group and model groups were given constant volume of DMSO intragastrically， every 12 h， for consecutive 7 d. The neurological deficits were evaluated with modified Longa score； HE staining was performed to observe the pathological changes of cerebral tissue in rats； the area of cerebral infarction was measured by TTC， and the percentage of cerebral infarction area； TUNEL staining was performed to detect apoptotic neurons. The expression of CD34， VEGF and DLL4 were detected by immunofluoresence and immunoblotting assay， respectively. RESULTS： Compared with sham operation group， the number of cortical cells in the model group decreased and arranged irregularly， with obvious infarct area and obvious decrease of neovascularization； the neurological deficit score， the percentage of cerebral infarction area and TUNEL positive cells increased significantly， while the expression of CD34， VEGF and DLL4 decreased significantly （P＜0.05 or P＜0.01）. Compared with model group， the above symptoms of the rats in each administration group were significantly improved， the neurological deficit score， the percentage of cerebral infarction area and the number of TUNEL positive cells were significantly reduced； the expression levels of CD34， VEGF and DLL4 were significantly increased； the neurological deficit score， the percentage of cerebral infarction area and the number of TUNEL positive cells in Z-GL+AKBA high-dose group were significantly lower or less than low dose group； the expression of CD34 and DLL4 in high-dose group was significantly higher than low-dose group （P＜0.05 or P＜0.01）. CONCLUSIONS： Z-GL combined with AKBA can relieve neurological deficit and cerebral injury of cerebral ischemia-reperfusion injury model rats， which may be related to promoting angiogenesis and up-regulating the expression of VEGF and DLL4 protein， with a certain dose-dependent effect. |
| 期刊： | 2019年第30卷第24期 |
| 作者： | 汪继涛，刘天龙，李玉文 |
| AUTHORS： | WANG Jitao，LIU Tianlong，LI Yuwen |
| 关键字： | 脑缺血再灌注损伤；Z-没药甾酮；11-羰基-β-乙酰乳香酸；血管新生；血管内皮生长因子；神经功能缺损；大鼠 |
| KEYWORDS： | Cerebral ischemia-reperfusion injury； Z-guggulsterone； Acetyl-11-keto-β-boswellic acid； Angiogenesis； VEGF； Neurological deficit； Rats |
| 阅读数： | 395 次 |
| 本月下载数： | 11 次 |
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