Study on expression of RYR2, FKBP12.6 and CaMK-II in lung tissue of patients with chronic obstructive pulmonary disease

Xi Wang, Ping Li, B. Zhuan, Qun Yuan, Jun Xie, Zhao Yang
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Abstract

Objective To explore the significance of immunohistochemical expression of Ryanodine receptor 2 (RYR2), FK506-binding protein 12.6 (FKBP12.6) and Calcium/ calmodulin dependent protein kinaseⅡ (CaMK-Ⅱ) in lung tissues from patients with chronic obstructive pulmonary disease (COPD). Methods A retrospective analysis from November 2012 to April 2017 in People′s Hospital of Ningxia Hui Autonomous Regin, lung tissue of 30 patients after lung cancer surgery, according to the results of pulmonary function test and Cardio-Uhrasonography, the patients were divided into three groups: COPD with pulmonary hypertension (PH)(group A) and COPD group (group B), non-COPD, non-PH patients with pulmonary tumor as the negative control group (group C). Take lung tissue about 5 cm from the cancerous area was removed after surgery.The Circum-ferential area of pulmonary valve of the three groups has been observed.To observe RYR2, FKBP12.6 and CaMK-Ⅱby immunohistochemical method respectively, then make correlation analysis. Results (1)Compared with group C, wall area% (WA%), pulmonary artery systolic pressure (PASP) were higher in group A and group B (F=24.115, 9.421, both P<0.05), and WA%, PASP were higher in group A than group B. (2)Compared with group C, the immunohistochemical expressions of RYR2, FKBP12.6 and CaMK-Ⅱ in group A and group B were all increased (F=9.219, 6.143, 11.337, all P<0.05), and the immunohistochemical expressions of RYR2, FKBP12.6 and CaMK-Ⅱ in group A was higher than group B. (3)Correlation analysis indicated that the immunohistochemical expressions of RYR2 in group A and B was positively correlated with WA% (r=0.547, 0.771, both P<0.01), while the immunohistochemical expressions of RYR2 in group A was positively correlated with PASP (r=0.773, P<0.01). Histochemical expressions of FKBP12.6 in group A were positively correlated with WA% (r=0.796, 0.810, both P<0.01), and the immunohistochemical expressions of FKBP12.6 in group A was positively correlated with PASP (r=0.729, P<0.01). The immunohistochemical expressions of CaMK-Ⅱ in group A and B were positively correlated with WA% (r=0.879, 0.504, both P<0.01), and the immunohistochemical expressions of CaMK-Ⅱ in group A was positively correlated with PASP (r=0.748, P<0.01). Conclusions FKBP12.6 and CaMK-Ⅱ may play a role in COPD-related pulmonary artery proliferation. Key words: Pulmonary disease, chronic obstructive; Hypertension, pulmonary; Ryanodine receptor calcium release channel; Calcium-calmodulin-dependent protein kinase type 2; FK506-binding protein 12.6
慢性阻塞性肺疾病患者肺组织中RYR2、FKBP12.6和CaMK-II表达的研究
目的探讨慢性阻塞性肺疾病(COPD)患者肺组织中Ryanodine受体2 (RYR2)、fk506结合蛋白12.6 (FKBP12.6)和钙/钙调素依赖性蛋白激酶Ⅱ(CaMK-Ⅱ)免疫组化表达的意义。方法回顾性分析2012年11月至2017年4月宁夏回族自治区人民医院收治的30例肺癌术后肺组织患者,根据肺功能检查及超声心动图结果,将患者分为3组:COPD合并肺动脉高压(PH)组(A组)、COPD组(B组)、非COPD、非PH合并肺肿瘤患者作为阴性对照组(C组)。术后取距癌区约5cm的肺组织切除。观察三组患者肺动脉瓣围周面积。采用免疫组化方法分别观察RYR2、FKBP12.6和CaMK-Ⅱ,并进行相关性分析。结果(1)与C组比较,A组和B组的壁面积% (WA%)、肺动脉收缩压(PASP)均高于B组(F=24.115、9.421,均P<0.05), A组的WA%、PASP均高于B组(2)与C组比较,A组和B组的RYR2、FKBP12.6、CaMK-Ⅱ免疫组化表达均升高(F=9.219、6.143、11.337,均P<0.05), RYR2、A组FKBP12.6、CaMK-Ⅱ均高于B组。(3)相关性分析显示,A组和B组RYR2免疫组化表达与WA%呈正相关(r=0.547、0.771,均P<0.01), A组RYR2免疫组化表达与PASP呈正相关(r=0.773, P<0.01)。A组FKBP12.6的组织化学表达与WA%呈正相关(r=0.796, 0.810,均P<0.01), A组FKBP12.6的免疫组织化学表达与PASP呈正相关(r=0.729, P<0.01)。A、B组CaMK-Ⅱ免疫组化表达与WA%呈正相关(r=0.879、0.504,均P<0.01), A组CaMK-Ⅱ免疫组化表达与PASP呈正相关(r=0.748, P<0.01)。结论FKBP12.6和CaMK-Ⅱ可能在copd相关肺动脉增生中起作用。关键词:肺部疾病;慢性阻塞性肺疾病;高血压、肺;赖诺定受体钙释放通道;钙钙调素依赖性蛋白激酶2型;fk506结合蛋白
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