二酰基甘油类似物OAG对压力超负荷大鼠心肌细胞瞬时受体电位通道C亚族3型及钙调神经磷酸酶的影响

Effects of 1-oleoyl-2-acetyl-sn-glycerol on expression of transient receptor potential canonical channel and calcineurin in rat hypertrophic cardiomyocytes induced by pressure overload

目的探讨瞬时受体电位通道C亚族3型(TRPC3)激动剂二酰基甘油类似物1-oleoyl-2-acetyl-sn-glycerol(OAG)对压力超负荷诱导大鼠左心室肥厚心肌组织TRPC3及钙调神经磷酸酶Aβ(calcineurinAβ,CaNAβ)表达的影响。方法采用腹主动脉缩窄(AAC)方法构建成年雄性SD大鼠左心室肥厚模型。12只假手术和12只模型大鼠分别随机分为假手术组、假手术+OAG组、AAC组、AAC+OAG组(每组6只)。术后假手术+OAG组和AAC+OAG组分别腹腔注射TRPC3特异性激动剂OAG。给药4周后检测各组大鼠血压、左心室质量指数(LVMI)、左心室心肌细胞横径(LVTDM);RT-PCR、Westernblot及免疫组化检测TRPC3、CaNAβ的mRNA和蛋白表达。结果 AAC组血压、LVMI和LVTDM均高于假手术组[(170.7±9.3)比(114.7±8.4)mmHg,(2.77±0.11)比(1.94±0.05)mg/g,(17.96±0.98)比(14.08±0.85)μm,P<0.05],AAC+OAG组较AAC组和假手术+OAG组以上各指标明显增高(P<0.05)。4个组均有TRPC3和CaNAβ的表达,AAC组TRPC3和CaNAβ的mRNA和蛋白表达高于假手术组(P<0.05),AAC+OAG组较AAC组和假手术+OAG组的TRPC3和CaNAβ表达增高(P<0.05)。结论 AAC大鼠左心室心肌细胞TRPC3和CaNAβ较假手术组表达上调;OAG可能促进压力超负荷大鼠心肌细胞TRPC3表达,激活钙离子依赖的CaNAβ,参与心肌肥厚的进展。

Objective To investigate the effect of transient receptor potential canonical 3 （TRPC3） agonist 1-oleoyl- 2 acetyl-sn-glycerol （OAG） on expression of TRPC3 channel and caleineurin AI3 （CaN Aβ） in hypertrophic cardio myocytes induced by pressure overload. Methods Left ventricular hypertrophy models was induced by abdominal aorta constriction （AAC） in male adult Sprague-Dawley rats. 12 Male Sprague-Dawley model rats and 12 sham op- eration （SO） rats were randomly divided into SO group, SO＋ OAG group, abdominal aorta constriction （AAC） group, and AAC＋OAG group, n=6 in each group. After 4 weeks of OAG administrated, blood pressure, left ventricular mass index （LVMI）, left ventricular transdiameter （LVTDM） of eardiomyocyte were examined. RT-PCR and Western blot were used to detect the expression of TRPC3 and CaN Aβ mRNA and protein. Results Compared with SO group, blood pressure, LVMI and LVTDM were significantly higher in AAC group [（ 170.7±9.3） vs （114.7±8.4） mmHg, （2.77±0.11） vs （1.944±0.05） mg/g, （17.96±0.98） vs （14. 08±0. 85）μm, P〈0.05], those in AAC＋OAG group were dramatically higher （P〈0.05） compared with AAC or SO＋ OAG group. Expressions of TRPC3 and CaN Aβ mRNA and protein were discovered in all groups, but in AAC group those were significantly higher compared with SO group, and those increased significantly in AAC＋ OAG group （P〈0.05） compared with AAC or SO＋OAG group. Conclusion Expressions of TRPC3 and CaN Aβ mRNA and proteinin AAC group were significantly higher compared with SO group. TRPC3 and CaN Aβ may participate in the process of left ventricular hypertrophy. OAG may promote TRPC3 expression in the pathphysiological progress of myocardial hypertrophy induced by pressure overload through activating calcium-dependent CaN Aβ in rats.