Shanghai International Medical Center, China.
Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, China.
Adv Clin Exp Med. 2021 Aug;30(8):823-829. doi: 10.17219/acem/135510.
Cerebrovascular disease is currently a serious threat to human health and life, commonly including cerebral infarction, cerebral hemorrhage and transient cerebral ischemia, among others.
To explore the role and e molecular mechanism of GP6 in the development of cerebral ischemic stroke (CIS) induced by atherosclerosis (AS).
Forty-five male New Zealand white rabbits were randomly divided into 3 groups: the control, CIS model and anti-GP6 group. Carotid artery tissues and blood of the white rabbits were collected for analysis. Hematoxylin and eosin (H&E) staining was used to analyze the pathological characteristics of vascular endothelial injury. Flow cytometry (FCM) was performed to analyze the content of Th1 and Th17 in blood. Immunohistochemistry was used to analyze the distribution and relative expression of FCER1G, ITGA2 and GP6 proteins in the carotid artery and cerebrovascular tissues. Western blot was applied to determine the protein expression of GP6, FYN, PKA, pPTK2, and pFAK1 in carotid artery tissues of the rabbits.
In the CIS model group, there was lymphocyte infiltration, fibrous tissue formation, and the formation of thrombus and lipid plaques. In the anti-GP6 group, scattered thin plaques were observed, and no obvious foam cell deposition was observed. The Th1 and Th17 content was significantly decreased in the CIS model group compared to the control and anti-GP6 group. The relative expression of FCER1G, ITGA2 and GP6 in the CIS model group was significantly higher compared to those in the control group and anti-GP6 group. The protein expression of GP6, FYN, PKA, pPTK2, and pFAK1 in the CIS model group were markedly higher compared to those in the control group and anti-GP6 group.
GP6 can promote the development of CIS by activating the FYN-PKA-pPTK2/FAK1 signaling pathway.
脑血管病目前严重威胁人类健康和生命，常见的有脑梗死、脑出血和短暂性脑缺血发作等。
探讨糖蛋白 6（GP6）在动脉粥样硬化（AS）所致脑缺血性卒中（CIS）中的作用及其分子机制。
45 只雄性新西兰大白兔随机分为 3 组：对照组、CIS 模型组和抗-GP6 组。收集各组大白兔颈动脉组织和血液进行分析。苏木精-伊红（H&E）染色分析血管内皮损伤的病理特征。流式细胞术（FCM）分析血液中 Th1 和 Th17 的含量。免疫组化分析颈动脉和脑血管组织中 FCER1G、ITGA2 和 GP6 蛋白的分布和相对表达。Western blot 检测各组大白兔颈动脉组织中 GP6、FYN、PKA、pPTK2 和 pFAK1 蛋白的表达。
CIS 模型组可见淋巴细胞浸润、纤维组织形成，血栓及脂质斑块形成；抗-GP6 组可见散在的薄斑块，未见明显泡沫细胞沉积。与对照组和抗-GP6 组相比，CIS 模型组 Th1 和 Th17 含量明显降低。CIS 模型组 FCER1G、ITGA2 和 GP6 的相对表达均明显高于对照组和抗-GP6 组。CIS 模型组 GP6、FYN、PKA、pPTK2 和 pFAK1 蛋白表达明显高于对照组和抗-GP6 组。
GP6 可通过激活 FYN-PKA-pPTK2/FAK1 信号通路促进 CIS 的发生发展。
