Objective: To explore the effect and potential mechanism of cardiac adipose triglyceride lipase (ATGL) overexpression on burn-induced cardiac injury. Methods: Eight-week-old C57BL/6J mice with cardiac ATGL overexpression driven by the myosin heavy chain (MHC) promoter (MHC-ATGL burn group) and wild-type (wild-type burn group) mice were randomly chose to the following experiments with burn injury after 24 h (n=8/group), MHC-ATGL mice and wild-type mice with corresponded age and sex were included as control. Cardiac ATGL protein expression, serum levels of cardiac troponin T and cardiac kinase-MB (CK-MB), cardiac free fatty acid and reactive oxygen species were detected. The wild-type and MHC-ATGL burn groups were not only compared with their corresponded control groups, but also compared between each other. Results: The hair color and development were shown little difference between each group. ATGL protein expression is elevated in wild-type burn group (1.00±0.68 vs 3.09±0.93, P=0.023) and decreased in MHC-ATGL burn group (17.84±2.41 vs 10.36±2.22, P<0.001), while ATGL protein expression is still increased in MHC-ATGL burn group compared with wild-type burn group (P<0.001). Serum levels of cardiac troponin T and CK-MB were both elevated in wild-type burn group and MHC-ATGL burn group [(0.456±0.131) vs (0.076±0.019) μg/L and (0.219±0.089) vs (0.060±0.019) μg/L, (1 421±162) vs (221±67) U/L and (761±142) vs (221±41) U/L] (all P<0.001), while serum levels of cardiac troponin T and CK-MB was still decreased in MHC-ATGL burn group compared with wild-type burn group (P<0.001). In addition, cardiac free fatty acid was increased in wild-type burn group and little difference was found in MHC-ATGL burn group [(2.54±0.51) vs (0.46±0.27) mmol/L, P<0.001, and (0.81±0.38) vs (0.59±0.25) mmol/L, P=0.251], while cardiac free fatty acid was significant reduction in MHC-ATGL burn group compared with wild-type burn group (P<0.001). Levels of cardiac reactive oxygen species was both elevated in wild-type burn group and MHC-ATGL burn group [(1.89±0.23) vs (1.00±0.18) and (1.38±0.17) vs (0.95±0.13)] (both P<0.001), while levels of cardiac reactive oxygen was reduction in MHC-ATGL burn group compared with wild-type burn group (P<0.001). Conclusion: Cardiac ATGL overexpression may protect against burn-induced cardiac injury through reducing free fatty acid and reactive oxygen species production.
目的: 探讨心脏过表达三酰甘油脂肪酶(ATGL)对烧伤后小鼠心肌损害的影响及可能机制。 方法: 随机选取8周龄心肌肌球蛋白重链(MHC)启动子驱动的心脏过表达ATGL雄性小鼠(MHC-ATGL烫伤组)和野生型雄性C57BL/6J小鼠(野生型烫伤组)构建烫伤模型,以同周龄和同性别的MHC-ATGL假烫伤小鼠(MHC-ATGL对照组)和野生型C57BL/6J假烫伤小鼠(野生型对照组)作为对照,每组8只。烫伤24 h后取材进行实验。分别检测心脏组织中ATGL蛋白表达水平、血清心肌肌钙蛋白T、肌酸激酶同工酶、心脏组织游离脂肪酸含量和心脏组织活性氧水平。两烫伤组分别与其对照组进行比较,两烫伤组间同时进行比较。 结果: 各组小鼠毛发颜色和生长发育无明显差异。野生型烫伤组心脏ATGL蛋白表达显著升高(1.00±0.68比3.09±0.93,P=0.023),而MHC-ATGL烫伤组心脏ATGL蛋白表达明显下降(17.84±2.41比10.36±2.22,P<0.001),但MHC-ATGL烫伤组心脏ATGL蛋白表达仍显著高于野生型烫伤组(P<0.001)。野生型烫伤组和MHC-ATGL烫伤组血清心肌肌钙蛋白T、血清肌酸激酶同工酶均显著高于其对照组[(0.456±0.131)比(0.076±0.019)μg/L和(0.219±0.089)比(0.060±0.019)μg/L、(1 421±162)比(221±67)U/L和(761±142)比(221±41)U/L](均P<0.001),而MHC-ATGL烫伤组血清心肌肌钙蛋白T、血清肌酸激酶同工酶均显著低于野生型烫伤组(均P<0.001);野生型烫伤组心脏组织游离脂肪酸含量显著高于其对照组[(2.54±0.51)比(0.46±0.27)mmol/L](P<0.001),MHC-ATGL烫伤组无明显变化[(0.81±0.38)比(0.59±0.25)mmol/L](P=0.251),而MHC-ATGL烫伤组心脏游离脂肪酸含量显著低于野生型烫伤组(P<0.001)。野生型烫伤组和MHC-ATGL烫伤组心脏组织活性氧水平均显著高于其对照组[(1.89±0.23)比(1.00±0.18)和(1.38±0.17)比(0.95±0.13)](均P<0.001),而MHC-ATGL烫伤组心脏组织活性氧水平显著低于野生型烫伤组(P<0.001)。 结论: 心脏过表达ATGL可能通过降低游离脂肪酸和活性氧生成减轻烧伤后心肌损害。.
Keywords: Adipose triglyceride lipase; Burns; Cardiac injury; Fatty acids, nonesterified; Reactive oxygen species.