高同型半胱氨酸血症亲代对子代肝组织线粒体生物合成的影响

Effects of hyperhomocysteinemia of parental generation on mitochondrial biosynthesis in liver tissue of filial generation

目的探讨高同型半胱氨酸血症亲代对子代肝组织线粒体代谢的影响。方法将2只雄性小鼠和6只雌性小鼠分别随机等分为对照组和实验组,雌雄分笼饲养,实验组饲喂含1%甲硫氨酸饲料,对照组饲喂普通饲料,4周后合笼,待雌鼠产下子代后,颈椎离断法处死亲代,取亲代外周血0.5 mL,全自动生化仪测量血浆同型半胱氨酸(Hcy)水平,取肝组织5 mg。从2组每只雌性小鼠的子代中随机选取3只新生小鼠,每组9只,即实验组子代和对照组子代,取子代小鼠肝脏组织5 mg,实时荧光定量PCR法检测亲代和子代小鼠肝组织中过氧化物酶体增殖物激活受体γ共激活因子-1α(PGC-1α)、线粒体转录因子-A(TFAM)基因表达水平和线粒体DNA拷贝数。结果实验组亲代小鼠血浆Hcy水平和肝组织中PGC-1α、TFAM基因表达水平均明显高于对照组亲代小鼠(P均<0.05),子代数量明显少于对照组(P<0.05),肝组织中线粒体DNA拷贝数与对照组比较差异无统计学意义(P>0.05)。实验组子代小鼠肝组织中PGC-1α、TFAM基因表达水平和线粒体DNA拷贝数均明显低于对照组子代小鼠(P均<0.05)。结论亲代患高同型半胱氨酸血症对自身肝组织线粒体代谢影响较小,但可抑制子代肝脏组织线粒体生物合成。

Objective It is to investigate the effect of hyperhomocysteinemia(HHcy)on mitochondrial metabolism in filial generation.Methods Two male mice and six female mice were randomly divided into control group and experimental group.The males and females were divided according to their gender and fed in cages.The experimental group was fed with the diet containing 1%methionine,the control group was fed with common diet.The male and female mice were caged together in 4 weeks later.After the female rats were born,the parents were killed by cervical vertebra amputation method,their 0.5 mL of peripheral blood was taken to detect the concentration of plasma homocysteine(Hcy)by automatic biochemical instrument,and 5 mg liver tissue was taken.3 newborn mice were randomly selected from the filial generation of each female mouse in each group,with 9 mice in each group,that was the filial generation of the experimental group and the control group,and 5 mg liver tissue of the filial generation was taken.The copy number of mitochondrial DNA and the expression of peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α)and mitochondrial transcription factor A(TFAM)genes in liver tissues of the parental and filial generation were detected by real-time PCR.Results The plasma Hcy level and the expression levels of PGC-1αand TFAM genes in the parental mice of the experimental group were significantly higher than those of the parental mice of the control group(P<0.05),and the number of offspring of the experimental group was significantly less than that of the control group(P<0.05),the copy number of mitochondrial DNA in liver tissue was not significantly different from that in the control group(P>0.05).The expression levels of PGC-1α,TFAM gene and mitochondrial DNA copy number in the liver tissues of the offspring of the experimental group were significantly lower than those of the offspring of the control group(all P<0.05).Conclusion Parental HHcy has little effect on the metabolism of mitochondria in their own liver tissues,but can inhibit the biosynthesis of mitochondria in the liver tissues of their offspring.