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目的探讨转化生长因子β(transforming growth factorβ,TGF-β)、结缔组织生长因子(connective tissue growth factor,CTGF)在低压缺氧条件下发生右心室心肌纤维化与肥大中的作用。方法将50只8周龄雄性SD大鼠[体质量(188.6±19.3)g]随机分为常氧喂养对照组与低压缺氧喂养3、7、14和28 d实验组(n=10),低压缺氧大鼠置于模拟海拔6 000 m的低压舱内饲养。分离右心室,称量法计算右心室肥厚指数。采用荧光定量PCR与免疫印迹法分别检测右心室心肌组织中Ⅰ型胶原、TGF-β和CTGF的mRNA与蛋白表达水平,并分析低压缺氧相同天数TGF-β和CTGF与Ⅰ型胶原表达水平、右心室肥厚指数的相关性。结果与常氧组相比,右心室心肌组织中低压缺氧各组右心室肥厚指数均升高,其中低压缺氧7、14、28 d组右心室肥厚指数显著升高(P<0.05)。与常氧组相比,右心室心肌组织中低压缺氧各组Ⅰ型胶原水平均升高,其中低压缺氧7、14、28 d组水平显著升高(P<0.05)。与常氧组相比,低压缺氧3 d组右心室心肌组织中TGF-β(3.68±0.17)、CTGF(8.73±0.96)蛋白表达量均显著升高(P<0.05),低压缺氧28 d组右心室心肌组织中TGF-β(0.93±0.15)、CTGF(12.62±0.14)蛋白水平均显著升高(P<0.05),而低压缺氧7、14 d组两细胞因子表达量与对照组比较差异无统计学意义(P>0.05)。随低压缺氧时间增加,右心室心肌组织中两生长因子mRNA表达水平与右心室肥厚指数呈显著正相关(P<0.05),与Ⅰ型胶原的mRNA水平也呈显著正相关(P<0.05,低压缺氧28 d组除外);随低压缺氧时间增加,TGF-β的mRNA水平与CTGF的mRNA水平呈显著正相关(P<0.05)。结论随低压缺氧时间增加,右心室心肌组织中TGF-β、CTGF先增加后降低再增加的表达变化,参与了低压缺氧时右心室心肌纤维化、心肌肥大的过程。
Objective To investigate the effects of transforming growth factor β (TGF-β) and connective tissue growth factor (CTGF) on right ventricular fibrosis and hypertrophy induced by hypobaric hypoxia. Methods Fifty eight-week-old male Sprague Dawley rats [body weight (188.6 ± 19.3) g] were randomly divided into normoxic feeding control group and hypobaric hypoxia fed 3, 7, 14 and 28 d experimental groups (n = 10) Hypobaric hypoxic rats were housed in a low pressure cabin simulating an altitude of 6 000 m. Right ventricular separation, weighing method to calculate the right ventricular hypertrophy index. The mRNA and protein expression of type Ⅰ collagen, TGF-β and CTGF in right ventricular myocardium were detected by real-time PCR and Western blotting respectively. The expression of TGF-β, CTGF and type Ⅰ collagen in hypobaric hypoxia and hypoxia were analyzed. Right ventricular hypertrophy index correlation. Results Compared with normoxia group, right ventricular hypertrophy index increased in hypoxic hypoxia group, and right ventricular hypertrophy index in hypoxia hypoxia group increased significantly on day 7, day 14 and day 28 (P <0.05). Compared with normoxia group, the level of type I collagen in hypoxic hypoxia groups in right ventricular myocardium increased, especially in hypoxia 7,14,28 d group (P <0.05). Compared with normoxia group, the protein expression of TGF-β (3.68 ± 0.17) and CTGF (8.73 ± 0.96) in right ventricular myocardium in hypoxia hypoxia 3 d group were significantly increased (P <0.05) The protein levels of TGF-β (0.93 ± 0.15) and CTGF (12.62 ± 0.14) in right ventricular myocardium of d group were significantly increased (P <0.05), while the expression of two cytokines in hypoxia group There was no significant difference between the two groups (P> 0.05). With the increase of hypobaric hypoxia time, the mRNA expression of two growth factors in right ventricular myocardium was positively correlated with right ventricular hypertrophy index (P <0.05), and positively correlated with type Ⅰ collagen mRNA (P <0.05, (P <0.05). With the increase of hypobaric hypoxia time, the mRNA level of TGF-βwas positively correlated with the mRNA level of CTGF (P <0.05). Conclusion With the increase of hypobaric hypoxia time, the expression of TGF-β and CTGF in the right ventricular myocardium increases first, then decreases and then increases, which is involved in the process of right ventricular fibrosis and cardiac hypertrophy during hypobaric hypoxia.