高血压患者胆囊动脉重构及钙调控相关基因改变

The remodeling of gallbladder artery and altered expression of calcium handling genes in hypertensive patients

  • 摘要: 目的观察高血压患者胆囊动脉的形态结构变化,探讨钙调控相关基因参与重构的可能机制。方法选择2011年6月至2012年3月于遵义医学院附属医院肝胆外科行胆囊切除术的21例胆结石患者,根据血压水平分为对照组(n=11)和高血压组(n=10),分别用HE染色、Masson染色观察动脉形态结构,利用计算机辅助图像分析系统测定内膜中层厚度(IMT)、内膜和中膜横截面积(ICSA和MCSA),内中膜胶原纤维容积分数(CVF),免疫组化染色检测α平滑肌肌动蛋白(α-SMA)、增殖细胞核抗原(PCNA)在胆囊动脉的表达;real-time PCR检测胆囊动脉中膜平滑肌胚胎型肌球蛋白重链(SMemb)和钙调控相关基因mRNA的表达水平。结果与对照组相比,高血压组胆囊动脉IMT(79.5±4.7)比(51.2±4.3)μm、IMT与内径比值(0.25±0.02比0.17±0.01)、ICSA与内径比值(67.7±9.2比39.6±8.7)、MCSA与内径比值(242.4±20.7比153.3±19.7)增加(均P<0.05);内膜、中膜CVF(分别0.36±0.03比0.17±0.03;0.36±0.02比0.28±0.02;均P<0.05),细胞增殖指数(分别0.61±0.05比0.36±0.05;0.73±0.05比0.54±0.05;均P<0.05)增高;高血压组胆囊动脉中膜的SMemb基因,钠泵α1,瞬时受体电位(TRPC)1、3的基因表达升高,而钠泵α3、质膜钙泵亚型4的基因表达降低(均P<0.05)。结论高血压患者胆囊动脉发生重构,平滑肌细胞的表型转化和钙调控相关基因的转录异常可能参与重构。

     

    Abstract: Objective To observe the morphology changes of gallbladder arteries and investigate the mechanism of calcium handling genes involved in remodeling. Methods A total of 21patients with biliary calculus who underwent cholecystectomy at department of hepatobiliary surgery in Affiliated Hospital of Zunyi Medical College from Jun,2011to Mar,2012were divided into control group(n=11,normal blood pressure)and hypertensive group(n=10). HE staining and Masson staining were used to observe the morphology changes of arteries. The intimamedia thickness(IMT),intimal cross-sectional area(ICSA),medial cross-sectional area(MCSA),collagen volume fraction(CVF)of intimal and media were analyzed by computer image analysis system. The expression ofα-smooth muscle actin(α-SMA)and proliferating cell nuclear antigen(PCNA)were detected by immunohistochemical technique. The mRNA expression levels of embryonic smooth muscle myosin heavy chain(SMemb)and calcium handling genes were detected by realtime PCR. Results Compared with control group,IMT (79.5±4.7)vs(51.2±4.3)μm,IMT to internal diameter ratio(IMT/ID)(0.25±0.02vs 0.17±0.01),ICSA to internal diameter ratio(ICSA/ID)(67.7±9.2vs 39.6±8.7)and MCSA to internal diameter ratio(MCSA/ID)(242.4±20.7vs153.3±19.7)were increased in hypertensive group(all P<0.05);Compared with control group,in intima or media of artery,CVF(0.36±0.03vs 0.17±0.03;0.36±0.02vs 0.28±0.02,all P<0.05)and cell proliferation index(0.61±0.05 vs 0.36±0.05;0.73±0.05vs 0.54±0.05,all P<0.05)were increased in hypertension subjects;in media of artery,the mRNA expression of SMemb,sodium pumpα1subunit and transient receptor potential channels(TRPC)1,3were increased,while sodium pumpα3subunit and plasma membrane calcium-transporting ATPase 4were decreased in hypertensive group(all P<0.05). Conclusion This study provides evidences that hypertension is associated with the remodeling of the gallbladder artery. The phenotypic change of vascular smooth muscle cell and the abnormal expression of the calcium handling genes may play an important role in the arterial remodeling.

     

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