目的探讨磁共振成像(magnetic resonance imaging,MRI)联合血清γ-氨基丁酸受体相关蛋白2(GABA receptorassociated protein like 2,GABARAPL2)、锌指蛋白706(zinc finger protein 706,ZNF706)与BGCN同族体(within BGCNhomolog,WIBG)对...目的探讨磁共振成像(magnetic resonance imaging,MRI)联合血清γ-氨基丁酸受体相关蛋白2(GABA receptorassociated protein like 2,GABARAPL2)、锌指蛋白706(zinc finger protein 706,ZNF706)与BGCN同族体(within BGCNhomolog,WIBG)对早期类风湿关节炎(rheumatoid arthritis,RA)的诊断价值。方法选取2014年9月至2017年9月于本院就诊的260例RA患者为研究对象,根据病程将入选患者分为早期组(167例)和晚期组(93例),随机选取同期于本院体检的100例健康成人纳入对照组。分析RA患者的MRI征象,比较三组研究对象的血清GABARAPL2、ZNF706和WIBG水平,并采用受试者操作特征曲线的曲线下面积(receiver operating characteristic,AUC)评价其诊断价值。结果早期组和晚期组患者的骨质侵蚀、骨髓水肿和滑膜炎的发生率比较差异均无统计学意义(均P >0.05)。早期组患者血清GABARAPL2、WIBG和ZNF706水平均显著高于晚期组和对照组(均P <0.05);晚期组患者血清GABARAPL2、WIBG和ZNF706水平均显著高于对照组(均P <0.05)。在3个MRI征象中,骨髓水肿对早期RA的诊断价值最高,其次是滑膜炎与骨质侵蚀,三者的灵敏度较高,特异度较低,且三征象联合诊断的价值更高(Youden指数= 0.408)。血清WIBG水平对早期RA的诊断价值最高(AUC=0.708),其次是GABARAPL2(AUC=0.683)与ZNF706(AUC=0.662),三者的灵敏度较低,特异度较高,且三因子联合诊断的价值更高(Youden指数=0.495)。MRI联合血清GABARAPL2、ZNF706与WIBG对早期RA的诊断灵敏度、特异度分别为88.0%、68.9%,诊断价值最高(Youden指数=0.569)。结论 MRI联合血清GABARAPL2、ZNF706与WIBG能显著提高RA的早期诊断水平,值得临床推广应用。展开更多
BACKGROUND: The increased β-arrestin-2 and its combination with G-protein-coupled receptors (GPCRs) lead to GPCRs desensitization. The latter may be responsible for decreased contractile reactivity in the mesenteric ...BACKGROUND: The increased β-arrestin-2 and its combination with G-protein-coupled receptors (GPCRs) lead to GPCRs desensitization. The latter may be responsible for decreased contractile reactivity in the mesenteric arteries of cirrhotic patients and rats. The present study is to investigate the machinery changes of α-adrenergic receptors and G proteins and their roles in the contractility of mesenteric arteries of cirrhotic patients and animal models. METHODS: Patients with cirrhosis due to hepatitis B and cirrhotic rats induced by CCl 4 were studied. Mesenteric artery contractility in response to norepinephrine was determined by a vessel perfusion system. The contractile effect of G protein-coupled receptor kinase-2 (GRK-2) inhibitor on the mesenteric artery was evaluated. The protein expression of the α 1 adrenergic receptor, G proteins, β-arrestin-2, GRK-2 as well as the activity of Rho associated coiled-coil forming protein kinase-1 (ROCK-1) were measured by Western blot. In addition, the interaction of α 1 adrenergic receptor with β-arrestin-2 was assessed by co-immunoprecipitation. RESULTS: The portal vein pressure of cirrhotic patients and rats was significantly higher than that of controls. The doseresponse curve to norepinephrine in mesenteric arteriole was shifted to the right, and EC 50 was significantly increased in cirrhotic patients and rats. There were no significant differences in the expressions of the α 1 adrenergic receptor and G proteins in the cirrhotic group compared with the controls. However, the protein expressions of GRK-2 and β-arrestin-2 were significantly elevated in cirrhotic patients and rats compared with those of the controls. The interaction of the α 1 adrenergic receptor and β-arrestin-2 was significantly aggravated. This interaction was significantly reversed by GRK-2 inhibitor. Both the protein expression and activity of ROCK-1 were significantly decreased in the mesenteric artery in patients with cirrhosis compared with those of the controls, and this phenomenon was not shown in the cirrhotic rats. Norepinephrine significantly increased the activity of ROCK-1 in normal rats but not in cirrhotic ones. Norepinephrine significantly increased ROCK-1 activity in cirrhotic rats when GRK-2 inhibitor was used. CONCLUSIONS: β-arrestin-2 expression and its interaction with GPCRs are significantly upregulated in the mesenteric arteries in patients and rats with cirrhosis. These upregulations result in GPCR desensitization, G-protein dysfunction and ROCK inhibition. These may explain the decreased contractility of the mesenteric artery in response to vasoconstrictors.展开更多
基金supported by a grant from the National Natural Science Foundation of China (30972920)
文摘BACKGROUND: The increased β-arrestin-2 and its combination with G-protein-coupled receptors (GPCRs) lead to GPCRs desensitization. The latter may be responsible for decreased contractile reactivity in the mesenteric arteries of cirrhotic patients and rats. The present study is to investigate the machinery changes of α-adrenergic receptors and G proteins and their roles in the contractility of mesenteric arteries of cirrhotic patients and animal models. METHODS: Patients with cirrhosis due to hepatitis B and cirrhotic rats induced by CCl 4 were studied. Mesenteric artery contractility in response to norepinephrine was determined by a vessel perfusion system. The contractile effect of G protein-coupled receptor kinase-2 (GRK-2) inhibitor on the mesenteric artery was evaluated. The protein expression of the α 1 adrenergic receptor, G proteins, β-arrestin-2, GRK-2 as well as the activity of Rho associated coiled-coil forming protein kinase-1 (ROCK-1) were measured by Western blot. In addition, the interaction of α 1 adrenergic receptor with β-arrestin-2 was assessed by co-immunoprecipitation. RESULTS: The portal vein pressure of cirrhotic patients and rats was significantly higher than that of controls. The doseresponse curve to norepinephrine in mesenteric arteriole was shifted to the right, and EC 50 was significantly increased in cirrhotic patients and rats. There were no significant differences in the expressions of the α 1 adrenergic receptor and G proteins in the cirrhotic group compared with the controls. However, the protein expressions of GRK-2 and β-arrestin-2 were significantly elevated in cirrhotic patients and rats compared with those of the controls. The interaction of the α 1 adrenergic receptor and β-arrestin-2 was significantly aggravated. This interaction was significantly reversed by GRK-2 inhibitor. Both the protein expression and activity of ROCK-1 were significantly decreased in the mesenteric artery in patients with cirrhosis compared with those of the controls, and this phenomenon was not shown in the cirrhotic rats. Norepinephrine significantly increased the activity of ROCK-1 in normal rats but not in cirrhotic ones. Norepinephrine significantly increased ROCK-1 activity in cirrhotic rats when GRK-2 inhibitor was used. CONCLUSIONS: β-arrestin-2 expression and its interaction with GPCRs are significantly upregulated in the mesenteric arteries in patients and rats with cirrhosis. These upregulations result in GPCR desensitization, G-protein dysfunction and ROCK inhibition. These may explain the decreased contractility of the mesenteric artery in response to vasoconstrictors.
