| Objective Acute ischemic stroke is a serious disease that affects human health.Hyperhomocysteinaemia is one of the pathogenic factors of stroke.The metabolic,clinical phenotype and pathogenesis of homocysteine are not clear.The project explored the correlation between homocysteine(Hcy)and the TOAST of ischemic stroke,and the role that mitochondria play in ischemic stroke,providing a new theory information for the clinical diagnosis and treatment strategy.Methods(1)The case control studies of Hcy and TOAST type of Chinese ischemic stroke were selected in Chinese and English databases up to April 18,2018.All the data were analyzed using Stata software version 9.0(Stata Corp LP,College Station,TX).The standardized mean difference(SMD)and 95% confidence interval(CI)were used to compare continuous variables.(2)Thirty-two adult male SPF SD rats were randomly divided into Normal group(Normal,n = 8),Sham operation group(Sham,n = 8),MCAO group(n = 16).MCAO models were divided into the group with 2 hours after cerebral ischemia(MCAO-2h,n = 8)and the group with 4 hours after cerebral ischemia(MCAO-6h,n = 8).(2)The neurological condition was observed by Longa Neurologic function scoe test.The TTC and HE stains were used to observe the changes of brain histological.q PCR was used to analyze the mitochondrial copy numbers of nerve cells,and flow cytometry was used to detect the level of mitochondrial membrane potential.(3)The aerobic oxidation capacity and mitochondrial membrane potential level were analyzed respectively in RN-c and HT-22 cells treated by Hcy.Results(1)Hcy was was found as a risk for ischemic stroke(SMD = 1.15,95% CI= 0.85-1.45,P < 0.05)and all the TOAST types(LAA: SMD = 2.12,95% CI =1.40-2.84,P < 0.05;SAO: SMD = 1.10,95% CI = 0.72-1.48,P < 0.05;CE: SMD =1.17,95% CI = 0.64-1.71,P < 0.05;SOE: SMD = 0.88,95% CI = 0.53-1.24,P < 0.05;SUE: SMD = 1.50,95% CI = 0.66-2.33,P < 0.05),especially for the LAA(LAA vs SAO: SMD = 1.03,95% CI = 0.45–1.61,P < 0.05;LAA vs CE: SMD =1.54,95% CI= 0.60–2.48,P < 0.05;LAA vs SOE: SMD = 1.18,95% CI = 0.56–1.79,P < 0.05;LAA vs SUE: SMD = 1.42,95% CI = 0.47 – 2.37,P < 0.05).(2)TTC staining showed brain necrosis in MCAO group.The brain edema and nuclear shrinkage wereobserved in MCAO-2h HE staining.MCAO-6h brain cells showed obvious edema,nuclear separation and partial nuclear decomposition.The decrease level of membrane potential in MCAO-2h and MCAO-6h groups were significantly higher than that in control group(P<0.001).The decrease level of mitochondrial membrane potential in the MCAO-2h group was higher than that in the MCAO-6h group(P< 0.001).Mt DNA copy numbers in MCAO groups was significantly lower than that in normal group(P < 0.05).(3)After Hcy treatment,the oxygen consumption rate(OCR)of nerve cells decreased,and the OCR decreased most significantly within 5min.The OCR decrease was positively correlated with the treatment time and the Hcy concentration.Hcy affected the maximum respiratory function of RN-c and HT-22.There was no significant change in mitochondrial membrane potential level of ht-22 and rn-c cells after Hcy treatment(P > 0.05).Conclusion Hcy was a risk for ischemic stroke and all the TOAST types,especially for the LAA;Hcy may affect nerve cell function by interfering with the aerobic oxidative respiration capacity of mitochondria.Mitochondrial number changes and dysfunction may be an important factor affecting stroke disease progression and prognosis. |
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