目的探讨Twist相关蛋白1(Twist-related protein 1,TWIST1)对野百合碱(Monocrotaline,MCT)诱导的肺动脉高压(pulmonary arterial hypertension,PAH)大鼠肺血管重塑的影响及机制。方法将50只健康雄性SD大鼠,随机分为5组,即对照组、模型...目的探讨Twist相关蛋白1(Twist-related protein 1,TWIST1)对野百合碱(Monocrotaline,MCT)诱导的肺动脉高压(pulmonary arterial hypertension,PAH)大鼠肺血管重塑的影响及机制。方法将50只健康雄性SD大鼠,随机分为5组,即对照组、模型组、二甲基亚砜(Dimethyl sulfoxide,DMSO)溶剂处理的模型组、TWIST1抑制剂Harmine组、自噬抑制剂羟氯喹组。检测右心室收缩压(RVSP),右心室肥厚指数(RVHI)和内膜厚度百分比(MT%)以评估大鼠PAH的发展。采用免疫印迹法检测TWIST1,自噬相关蛋白LC3B以及RND3的蛋白质水平。结果与对照组比较,MCT诱导的PAH大鼠中TWIST1和LC3B表达增加,分别为对照组的2.32±0.22倍和0.87±0.19倍,差异具有统计学意义(t=15.812,11.227,均P<0.001);同时RND3表达下调,为对照组的0.32±0.07倍,差异具有统计学意义(t=-13.003,P<0.001)。给与TWIST1抑制剂Harmine或自噬抑制剂羟氯喹可显著抑制MCT诱导的自噬激活和RND3表达下调,同时降低了MCT诱导的PAH大鼠的RVSP,RVHI和MT%,差异具有统计学意义(t=-24.277~16.636,均P<0.001)。结论TWIST1通过诱导自噬激活促进肺血管重塑,促进PAH的发生发展。展开更多
Objective:The purpose of this study was to investigate the expression of Twist in salivary adenoid cystic carcinoma (SACC) and the relations between Twist expression and the clinicopathological characteristics. Method...Objective:The purpose of this study was to investigate the expression of Twist in salivary adenoid cystic carcinoma (SACC) and the relations between Twist expression and the clinicopathological characteristics. Methods: The expression of Twist was examined immunohistochemically in 48 cases of SACC, 18 of pleomorphic adenoma and 10 of normal parotid gland. The relationship between Twist expression in SACC and the clinicopathological factors was analyzed. Results: Twist expression was significantly higher in SACC tissues compared with pleomorphic adenomas and normal parotid gland tissues (P<0.05). Twist expression levels in SACC were significantly associated with histological type, perineural invasion, postoperative recurrence, and distant metastasis (P<0.05), rather than age, gender, tumor site, tumor size, or clinical staging (P>0.05). Conclusion: Twist expression may be associated with tumor cell differentiation, perineural invasion and metastasis of SACC. Twist expression is a potential prognostic factor for disease survival of SACC.展开更多
基金Supported by a grant from Science and Technology Project of Wenzhou City (No.Y20090055)
文摘Objective:The purpose of this study was to investigate the expression of Twist in salivary adenoid cystic carcinoma (SACC) and the relations between Twist expression and the clinicopathological characteristics. Methods: The expression of Twist was examined immunohistochemically in 48 cases of SACC, 18 of pleomorphic adenoma and 10 of normal parotid gland. The relationship between Twist expression in SACC and the clinicopathological factors was analyzed. Results: Twist expression was significantly higher in SACC tissues compared with pleomorphic adenomas and normal parotid gland tissues (P<0.05). Twist expression levels in SACC were significantly associated with histological type, perineural invasion, postoperative recurrence, and distant metastasis (P<0.05), rather than age, gender, tumor site, tumor size, or clinical staging (P>0.05). Conclusion: Twist expression may be associated with tumor cell differentiation, perineural invasion and metastasis of SACC. Twist expression is a potential prognostic factor for disease survival of SACC.