The Effects Of The Expression Of Acyl-CoA: Lysocardiolipin Acyltransferase 1 In Sciatic Nerves Of Diabetic Rats

Background and ObjectiveDiabetic neuropathy was one of the major chronic complications of diabetes, the pathogenesis of which had not been clearly elucidated. Recent studies suggested that oxidative stress was the key factor of diabetic complications. The reactive oxygen species were mainly produced in mitochondria, so the structures and functions of mitochondria would affect the level of oxidative stress. Cardiolipin(CL) was almost all located at the mitochondria, especially at the inner membrane, which maintained the morphology and functions of mitochondria. CL played an important role in the mitochondrial respiratory chain, mitochondrial fusion and fission, apoptosis and mitochondrial autophagy. Acyl-Co A: lysocardiolipin Acyltransferase 1(ALCAT1) was a key enzyme of cardiolipin pathological remodeling which could induce alterations of CL structures, contents and acyl chain compositions that were associated with mitochondrial dysfunction in several physiopathological conditions.The research aimed to discuss the association between ALCAT1 and diabetic neuropathy, and to observe the effect of oxidative stress on the expression of ALCAT1 by antioxidant intervention. Methods60 male rats were randomly divided into four groups: normal control group(NC), diabetes group for 4 weeks(D4), diabetes group for 8 weeks(D8) and antioxidant group(AO). All the rats were diabetic models by injecting streptozotocin except NC. The sciatic nerve conduction velocity(s NCV) was measured, and the expressions of ALCAT1 in sciatic neurons were detected and electron microscope was used to observe the microstructure of neuron cell. Serum markers of oxidative stress such as superoxide dismutase, malondialdehyde and glutathione were also detected. Results1.The s NCV of NC, D4, D8 and AO was(56.56±4.40m/s)vs(53.43±4.25m/s)vs(41.90±3.79m/s)vs(53.38±3.26m/s).2. The expressions of ALCAT1 m RNA were((0.92±0.08)*10-2)vs((1.38±0.12)*10-2)vs((2.57±0.24)*10-2)vs((1.34±0.09)*10-2)of group NC, D4, D8 and AO; western blot analysis: ALCAT1/β-actin in each group were( 0.56±0.04) vs(1.10±0.09)vs(1.56±0.13)vs(1.02±0.08).3. For group NC, D4, D8 and AO, the SOD(U/ml) levels were(56.72±3.75)vs(33.93±3.87)vs(25.50±2.33)vs(35.89±4.25); the MDA(nmol/ml) levels were(1.58±0.23)vs(3.84±0.41)vs(4.94±0.78)vs(3.48±0.37); and the GSH(mg GSH/l) levels were(17.63±1.42)vs(9.69±1.52)vs(5.80±1.69)vs(11.19±1.34).4. The microstructures of mitochondria and myelin were integral in group NC; as for D4 and D8, they all had pathological changes in different degrees, the mitochondrial structures of group D8 were seriously damaged. But group AO had slight changes in microstructures of neurons in sciatic fiber. Conclusions1. It lasts eight weeks for type I diabetic rats to suffer from diabetic peripheral neuropathy;2. The overexpression of ALCAT1 will remodel cardiolipin pathologically, causing mitochondrial dysfunction and increasing oxidative stress, then aggravating the development of diabetic neuropathy;3. Oxidative stress may regulate the expression of ALCAT1, and antioxidant treatment can slow the progression of diabetic neuropathy by downregulating the expression of ALCAT1.