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辅酶Q10对子痫前期孕鼠肝脏保护作用的研究

Study of coenzyme Q10 in the liver of preeclampsia pregnant rats

摘要目的:探讨辅酶Q10对子痫前期孕鼠肝脏的保护作用及其作用机制。方法选择50只孕鼠,随机(完全随机化法)分为子痫前期组(n=40)和正常妊娠组(n=10);于妊娠第10天开始建立子痫前期孕鼠模型,于妊娠第15~20天根据对子痫前期孕鼠处理方法的不同将子痫前期组进一步分为蒸馏水组、辅酶Q10组、辅酶Q10+硫酸镁组及硫酸镁组,每组均10只大鼠。(1)于妊娠第10、15、21天分别测量5组大鼠的鼠尾收缩压;于妊娠第10、15、21天进行24 h尿蛋白定量检测。(2)于妊娠第21天,采集5组孕鼠血液检测其肝功能包括丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)。(3)于妊娠第21天,采集5组孕鼠的肝脏标本,检测其肝组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、丙二醛(MDA)的含量及活化半胱氨酸天冬氨酸蛋白酶3(caspase-3)、Bcl-2及Bax蛋白的表达。结果(1)5组孕鼠血压、24 h尿蛋白定量的比较:妊娠第10天,5组孕鼠血压、24 h尿蛋白定量分别比较,差异均无统计学意义(P>0.05)。妊娠第15、21天,辅酶Q10组、辅酶Q10+硫酸镁组、硫酸镁组及蒸馏水组孕鼠血压、24 h尿蛋白定量均明显高于正常妊娠组(P<0.05);且妊娠第21天,辅酶Q10组、辅酶Q10+硫酸镁组、硫酸镁组孕鼠血压、24 h尿蛋白定量均明显低于蒸馏水组(P<0.05)。(2)5组孕鼠肝功能的比较:辅酶Q10组、辅酶Q10+硫酸镁组、硫酸镁组、蒸馏水组、正常妊娠组孕鼠血清ALT水平分别为(52±7)、(34±9)、(49±10)、(70±19)、(30±7)U/L,血清AST水平分别为(169±25)、(84±11)、(159±20)、(281±26)、(78±18)U/L,辅酶Q10组、硫酸镁组、蒸馏水组孕鼠血清ALT、AST水平均明显高于正常妊娠组(P<0.05);辅酶Q10+硫酸镁组孕鼠血清ALT、AST水平明显低于辅酶Q10组、硫酸镁组、蒸馏水组(P<0.05);辅酶Q10组、硫酸镁组孕鼠血清ALT、AST水平均明显低于蒸馏水组(P<0.05)。(3)5组孕鼠肝组织中SOD、GSH-PX、MDA含量及caspase-3、Bcl-2及Bax蛋白表达水平的比较:孕鼠肝组织中SOD含量,辅酶Q10组、辅酶Q10+硫酸镁组均明显高于硫酸镁组、蒸馏水组、正常妊娠组(P<0.05),硫酸镁组、蒸馏水组均明显低于正常妊娠组(P<0.05),硫酸镁组明显高于蒸馏水组(P<0.05)。辅酶Q10组、辅酶Q10+硫酸镁组、硫酸镁组、蒸馏水组分别与正常妊娠组比较,孕鼠肝组织中GSH-PX含量以及Bcl-2蛋白表达水平均明显降低(P<0.05),而MDA含量以及caspase-3、Bax蛋白表达水平均明显增高(P<0.05);辅酶Q10组、辅酶Q10+硫酸镁组、硫酸镁组分别与蒸馏水组比较,孕鼠肝组织中GSH-PX含量以及Bcl-2蛋白表达水平均明显增高(P<0.05),而MDA含量以及caspase-3、Bax蛋白表达水平均明显降低(P<0.05)。结论子痫前期孕鼠肝组织的氧化应激水平、细胞凋亡水平均升高;辅酶Q10可以有效改善子痫前期孕鼠的肝功能,减少肝细胞凋亡,具有保护肝脏的作用,其机制可能是通过抗氧化应激损伤和调节Bcl-2/Bax平衡从而抑制细胞凋亡。

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abstractsObjective To investigate the protective effect of coenzyme Q10 (CoQ10) in the liver of preeclampsiapregnant rats and the potential etiology. Methods Fifty pregnant SD rats were equally divided&nbsp;into the normal pregnant (NP) group (n=10) and the preeclampsia (PE) group (n=40) randomly. The PE rats (n=40) were equally divided into four groups randomly,distilled water(DW)group,CoQ10 group, CoQ10 combined magnesium(CM) group and magnesium (Mg) group were established by treating the preeclampsia rats on day 15 to 21 of gestation with different measures. As for all the 50 rats, systolic blood pressure (SBP) of rat tail was detected on day 10, 15 and 21 of gestation respectively, 24 hours proteinuria analysis were detected on day 10, 15 and 21 of gestation respectively, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in blood andsuperoxide dismutase (SOD), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), caspase-3, Bcl-2 and Bax protein expression in liver tissue were detected by western blot assay on day 21 of gestation. Results (1)SBP and 24 hours proteinuria analysis:there was no statistic difference among all the five groups on day 10 of gestation (P>0.05). Whereas, SBP and 24 hours proteinuria analysis were significantly higher in CoQ10 group, CoQ10 combined CM group, CM group and DW group than that in NP group on day 15, 21 of gestation (P<0.05). And SBP and 24 hours proteinuria analysis were significantly lower in CoQ10 group, CoQ10 combined CM group and CM group than that in DW group on day 21 of gestation (P<0.05). (2) Liver function: among CoQ10 group, CoQ10 combined CM group, CM group, DW group and NP group, serum levels of ALT were respectively(52±7),(34±9),(49±10), (70 ± 19),(30 ± 7)U/L;and serum levels of AST were respectively(169 ± 25),(84 ± 11),(159 ± 20),(281 ± 26)and(78±18)U/L. ALT and AST serum levels were significantly higher in CoQ10 group, CM group and DW group than that in NP group (P<0.05). ALT and AST serum levels were significant lower in CoQ10 combined CM group than those in CoQ10 group, CM group and DW group, respectively (P<0.05). ALT and AST serum levels were significant lower in CoQ10 group and CM group than that in DW group, respectively (P<0.05). (3) SOD, GSH-PX, MDA, caspase-3, Bcl-2 and Bax expression in liver tissue of rats: SOD expression was significant higher in CoQ10 group, CoQ10 combined CM group than thoes in CM group, DW group and NP group(P<0.05);SOD expression was significant lower in CM group, DW grouo than thoes in NP group(P<0.05);and SOD expression was significant higher in CM group than that in DW group(P<0.05). Compared with CoQ10 group, CoQ10 combined CM group, CW group and DW group respectively, the GSH-PX and Bcl-2 protein expressions were significant higher in NP group(P<0.05), while MDA, caspase-3 and Bax protein expressions were significant lower in NP group(P<0.05);compared with CoQ10 group, CoQ10 combined CM group and CW group respectively, the GSH-PX and Bcl-2 protein expressions were significant lower in DW group (P<0.05), while MDA, caspase-3 and Bax protein expressions were significant higher in DW group (P<0.05). Conclusions Oxidative stress and apoptosis levles were upregulated in PE pregnant liver tissues. CoQ10 could effectively protect the liver by improving the liver functions and decreasing the apoptosis of liver cells in PE pregnant rats, and markedly decrease the oxidative stress and apoptosis in the livers. The protective roles of CoQ10 in liver might through its function of anti-oxidative stress and inhibiting cell apoptosis by regulating the balance of Bcl-2/Bax.

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中华妇产科杂志

中华妇产科杂志

2016年51卷8期

608-615页

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