[摘要] 目的  探讨心磷脂酰基转移酶1（ALCAT1）与糖尿病周围神经病变(DPN)的关系。方法 雄性大鼠60只，随机分为正常对照 (NC) 组，糖尿病4周 (DW 4) 组，糖尿病8周 (DW 8) 组，抗氧化 (AO) 组。测各组坐骨神经传导速度(sNCV)，坐骨神经ALCAT1 mRNA和蛋白表达量，SOD 、MDA、谷胱甘肽(GSH)水平，以及坐骨神经电镜图。 结果   NC、DW 4、DW 8、AO组sNCV依次为（56.56±4.40）vs（53.43±4.25）vs（41.90±3.79）vs（53.38±3.26）m/s。DW 4、DW 8、AO组ALCAT1 mRNA表达量与NC组比较依次为（1.52±0.12）vs（2.86±0.30）vs（1.48±0.11）倍。NC、DW4、DW8、AO组ALCAT1蛋白相对表达量为（0.56±0.04）、（1.10±0.09）、（1.56±0.13）、（1.02±0.08）。NC、DW 4、DW 8、AO组SOD水平依次为（56.72±3.75）vs（33.93±3.87）vs（25.50±2.33）vs（35.89±4.25）U/ml；MDA水平依次为（1.58±0.23）vs（3.84±0.41）vs（4.94±0.78）vs（3.48±0.374）nmol/ml；GSH水平依次为（17.63±1.42） vs （9.69±1.52） vs （5.80±1.69） vs （11.19±1.34）mg/L。NC组神经元胞体、线粒体、髓鞘结构完整；DW 4组神经元肿胀、线粒体水肿、髓鞘板层开始散乱；DW 8组神经元肿胀明显、线粒体嵴断裂、髓鞘板层有囊性间隙出现；AO组神经元胞体胞体规则、线粒体肿胀、嵴较清晰、髓鞘与轴索间有轻微间隙出现。 结论 T1DM大鼠8周即进展为DPN。ALCAT1可能与DPN的发生发展机制相关。OS水平可能影响ALCAT1的表达。

[关键词] 糖尿病神经病变；心磷脂；氧化应激；线粒体功能障碍；心磷脂酰基转移酶1

Association analysis between ALCAT1 and Diabetic Peripheral Neuropathy LI Ya-kun, YANG Jun-peng, MA Xiang-xiang, et al. Department of Endocrinology and Metabolism,The People’s Hospital of Zhengzhou University, Zhengzhou 450003，China

Corresponding author：ZHAO Zhi-gang，E-mail：zhaozhigang1957@126.com

[Abstract] Objective To investigatethe relationship between Acyl-CoA:lysocardiolipin acyltransferase 1 (ALCAT1) and diabetic peripheral neuropathy. Methods  A total of 60 male rats were randomly divided into four groups:normal control group (NC), diabetes group of 4 weeks’duration(DW4), diabetes group of 8 weeks’ duration(DW8) and antioxidant treatment group (AO).The sciaticnerve conduction velocity (sNCV) was measured.The mRNA expressions and protein levels of ALCAT1 in sciatic neurons were detected. The electron microscope was used to observe the microstructures of neuron cells. SOD, MDA and GSH were also detected. Results  The sNCV of NC, DW4, DW8 and AO group were（56.56±4.40）vs（53.43±4.25）vs（41.90±3.79）vs（53.38±3.26）m/s.The expression of ALCAT1 mRNA were （1.52±0.12）vs（2.86±0.30）vs（1.48±0.11） times in DW4, DW8 and AO group as compared with NC group.The protein levels of ALCAT1 were （0.56±0.04）,（1.10±0.09）,（1.56±0.13）,（1.02±0.08）in NC, DW4,DW8 and AO group. The SOD levels were （56.72±3.75）vs（33.93±3.87）vs（25.50±2.33）vs（35.89±4.25）U/ml in NC, DW4,DW8 and AO group. The MDA levels were（1.58±0.23）vs（3.84±0.41）vs（4.94±0.78）vs（3.48±0.374）nmol/ml; and the GSH levels were （17.63±1.42）vs（9.69±1.52）vs（5.80±1.69）vs（11.19±1.34）mg/L in NC, DW4,DW8 and AO group respectively. The microstructures of neurons, mitochondria and myelin were normalin NC group.However, neurons swelling, mitochondria edema， myelin sheath broken could be seen in DW4 group.More seriously, advanced neurons swelling, mitochondria ridge broken, cystic space appearance in broken myelin sheath could be seen in DW8 group. In AO group, neurons were normal,mitochondria was edema but mitochondria ridge was clear, and slight space could be seen between myelin sheath and nerve axon. Conclusion   T1DM rats developed diabetic peripheral neuropathy after 8 weeks. ALCAT1 may be associated with the progress of diabetic peripheral neuropathy. Oxidative stress regulates the expression of ALCAT1.

[Keywords] Diabetic neuropathy（DPN）；Cardiolipin（CL）；Oxidative stress（OS）；Mitochondrial dysfunction；Acyl-CoA:lysocardiolipin acyltransferase 1(ALCAT1)