端粒重复因子2-P53信号通路在糖尿病心肌病中的作用

Role of telomeric repeat-binding factor 2-P53 signal pathway in diabetic cardiomyopathy

目的探讨端粒重复因子2-P53(TRF2-P53)信号通路在糖尿病心肌病(DCM)中的作用。方法体内研究予以链脲佐菌素(STZ)腹腔注射制造1型糖尿病小鼠模型,9周后超声检测明确DCM模型构建成功。小鼠心脏样本采用免疫印迹(WB)检测TRF2表达水平,采用免疫荧光检测P53表达水平。体外研究予以高糖刺激乳鼠心肌细胞,并采用WB检测TRF2表达水平,采用免疫荧光检测P53表达水平。TRF2 siRNA降低乳鼠心肌细胞TRF2的表达后,采用TUNEL检测凋亡情况,采用衰老相关-β-半乳糖苷酶(SA-β-gal)染色检测衰老情况,采用WB检测P53表达水平。结果体内研究发现,与WT小鼠相比,DCM小鼠TRF2表达下降,P53表达增加。体外研究发现,高糖刺激引起乳鼠心肌细胞TRF2表达下降,P53表达增加。TRF2 siRNA转染降低乳鼠心肌细胞TRF2水平后可促进凋亡和衰老,增加P53表达。结论TRF2-P53信号通路在DCM中起了重要的调控作用。

Objective To study the role of telomeric repeat-binding factor 2-P53(TRF2-P53)signal pathway in diabetic cardiomyopathy.Methods In vivo study,type 1 diabetes mouse model was induced by intraperitoneal injection of streptozocin(STZ).After 9 weeks,DCM model was successfully established.The expression level of TRF2 in mouse heart samples was detected by Western blot(WB)and P53 by immunofluorescence.In vitro studies,high sugar was given to stimulate the cardiac muscle cells of neonatal mice,TRF2 expression level was detected by WB and P53 expression level was detected by immunofluorescence.TRF2 siRNA was used to reduce the expression of TRF2 in neonatal mice cardiomyocytes,then TUNEL was used to detect apoptosis,SA-β-galactosidase(SA-β-gal)staining was used to detect condition of aging,and P53 expression level was detected by WB.Result In vivo studies found that TRF2 expression decreased and P53 expression increased in DCM mice compared with WT mice.In vitro studies showed that high glucose stimulation caused the decrease of TRF2 expression and the increase of P53 expression in cardiomyocytes of lactating rat.TRF2 siRNA transfection can promote apoptosis and senescence and increase P53 expression after reducing TRF2 level in cardiomyocytes of lactating rat.Conclusion TRF2-P53 signaling pathway plays an important role in the regulation of DCM.