| Objective:Study out Zuo Gui Wan pill intervention in pregnant rats hyperlipidemia model for its offspring glucose tolerance?IGT?reduction susceptible protein expression and its mechanism,the influence of the mother is to clear out pill intervention through what way to offspring IGT susceptible protein expression have long-term beneficial effects,and to further prevent or delay the onset of the offspring IGT.Methods:SD rats were randomly divided into 4 groups?each group of 12 female,male 6?,namely?1?normal control group,?2?the model control group,?3?insulin(4mg·kg-1)group,?4?ZGW(10g·kg-1)group.Model and insulin group and ZGW intervention group of pregnant rats using high fat feed feeding method to create the environment of hyperlipidemia.Building after a successful male and female 2:1 or cage for the night,pregnant rats on the third day?P3d?,insulin group according to 4mg·kg-1,muscle injection dosage,ZGW in 10g·kg-1lavage,normal given normal saline control group and model control group,the rats lavage group were according to20mL·kg-1,to P19d?due date?.Stay F0 surrogate rat after childbirth the F1,said rat body weight,take the F1 of F1generation of rat in each retain 12 per litter?6?,6??,group,and starting from the fifth week weighing F1 generation groups of rats weight every week.Starting from 10 weeks per week for each group rats on a glucose tolerance test?fasting glucose measurement first,then the corresponding dose of glucose to fill the stomach,2h after testing blood glucose levels?,to model group rats appeared IGT?7.8-11.2mmol/L tendency postprandial blood glucose level?,put to death between groups of rats,the right amount of plasma,the serum and tissue perfusion after take the organization,such as the pancreas,liver,using HE staining to observe each group pathological lesions of the liver and pancreas of rats;Using iTRAQ?isobaric Tag for Relative and Absolute Quantitation?technology for screening of different protein;Using RT-PCR technology to closely with IGT differences in protein is used to detect the mRNA expression level;ELISA method is used to detect ERK1 signaling pathways related indicators;Even from the view point of ERK1 pathway Zuo Gui Wan embryonic intervention IGT genetic susceptibility genes of IGT model rats and the influence of the differences in protein expression and its mechanism.Results:1.Compared with normal control group,the model induced by hyperlipidemia control group offspring?F1?in rats at different times after birth weight significantly reduced(*P<0.05,**P<0.01);Compared with model control group,insulin group and ZGW pill group in different time after birth weight increased significantly(#P<0.05,##P<0.01).2.Compared with normal control group,model control group of lipid four?TC,TG,HDL and LDL?levels and a significant rise in blood sugar levels?fasting and postprandial?(*P<0.05,**P<0.01);Compared with model control group,insulin group and ZGW for four levels and blood glucose levels of lipid in different degrees of improvement(#P<0.05,##P<0.01).3.Compared with normal control group,model control group of the liver and pancreatic tissue pathological slices showed fat kind change,congestion and islet atrophy of the organization;Compared with model control group,insulin group and ZGW to change fat samples,blood stasis and islet cell contraction eased.4.Proteomics analysis showed proliferation protein kinase-3?ERK1?is closely related to the metabolism of sugar,protein is IGT differences;Compared with normal control group,model control group of ERK1 were significantly reduced?P<0.05?;With the model,The control group,insulin group and ZGW bolus group ERK1 were significantly reduced?P<0.05?.5.Compared with normal control group,model control group in the F1 ERK1 mRNA expression level of rats significantly raised?*P<0.05?;Compared with model control group,insulin group and left to the F1 ERK1 mRNA expression level in rats had no significant difference.6.Compared with normal control group,model control group of beta 2,INS,INSR,PI3K significantly increased expression level(*P<0.05,**P<0.01),IRS1 expression level decreased significantly?*P<0.05?.Compared with model control group,insulin group beta 2,PI3K expression level decreased significantly?#P<0.05?,IRS1 expression level significantly increased?#P<0.05?,but the INS,INSR expression level not seen significantly reduced;Compared with model control group,left to bolus group of INS,INSR,PI3K expression level decreased significantly?#P<0.05?,IRS1 expression level significantly increased?#P<0.05?,but the expression of beta 2 levels not seen significantly reduced.Conclusion:ZGW to embryonic intervention can rats hyperlipidemia environment was born the F1 prevention and control of the onset of IGT produce certain effect,its mechanism might be:interaction between the body's own proteins,inhibition of ERK1whole way of expression result finally.ZGW pill nourishing kidney Yin,embryonic intervention had an epigenetic modification effect to the fetus,the body to another form of a balance of Yin and Yang,strengthening the adaptability of intrauterine fetal adverse environment,reduces the environment on the fetus of high sugar and high fat bad effects,reduce the risk of developing acquired IGT F1 generation of rats.And verifies the traditional Chinese medicine"The kidney stores essence","The main reproductive","The main growth"and"Yin ping yang mi,spirit is"basic theory. |
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