Therapeutic effect of Buzhong Yiqi decoction on gestational diabetes mellitus in pregnant rats and its inhibitory effect on susceptibility to diabetes in offspring

GAO Xin; ZHANG Yongbin; JIANG Yaojia

doi:10.3969/j.issn.1002-266X.2024.30.011

Abstract：Objective To observe the therapeutic effect of Buzhong Yiqi decoction on gestational diabetes mellitus(GDM)in pregnant rats and its inhibitory effect on susceptibility to diabetes in offspring,and to explore its possible mecha-nism of action.Methods Fifty SPF-grade healthy SD female pregnant rats were selected and randomly divided into the low-dose Buzhong Yiqi decoction(BZYQT-L)group,medium-dose Buzhong Yiqi decoction(BZYQT-M)group,high-dose Buzhong Yiqi decoction(BZYQT-H)group,GDM group,and control group,with 10 rats in each group.The GDM models were constructed by fasting for 12 h on the 7th day of gestation in four groups except the control group.After suc-cessful modeling,the pregnant rats in the BZYQT-L,BZYQT-M and BZYQT-H groups were given BZYQT by gavage at the doses of 2.84,5.67 and 11.34 g/kg,respectively,and the pregnant rats in the control group and the GDM group were giv-en an equal volume of normal saline,and each group was treated for 7 days,twice a day.Pregnant rats were taken from each group on the 7th,9th and 16th days of gestation,and the offspring were taken from each group at the age of 1,4 and 8 weeks,respectively,and the pancreatic tissues were isolated after collecting tail vein blood,and the serum glycosylated hemoglobin(GHb)and insulin(FINS)of pregnant rats and offspring in each group were detected by ELISA,and the ho-meostasis model assessment of insulin resistance(HOMA-IR)and insulin sensitivity index(ISI)were calculated,serum triglycerides(TG),total cholesterol(TC),low-density lipoprotein(LDL)and high-density lipoprotein(HDL)were mea-sured in pregnant rats and offspring of each group by automatic biochemical analyzer.Another five pregnant rats from each group were taken at gestation day of 18.5(late gestation)and were subjected to glucose tolerance test.The pancreatic tis-sues of pregnant rats and offspring in each group were taken,and the PPARGC1A mRNA and protein of pancreatic tissues were detected by qRT-PCR and Western blotting,respectively,and the methylation of PPARGC1A of pancreatic tissues was detected by bisulfite sequencing.Results Compared with the control group,the pregnant rats in the GDM group had higher levels of fasting blood glucose,area under the glucose tolerance curve(AUC),FINS,HOMA-IR,glycosylated he-moglobin(GHb),triglycerides(TG),total cholesterol(TC)and LDL,and lower levels of ISI and HDL(all P<0.05).Compared with the GDM group,the levels of fasting blood glucose,AUC,FINS,HOMA-IR,GHb,TG,TC and LDL were lower,and the levels of ISI and HDL were higher in pregnant rats of the BZYQT-L group,BZYQT-M group and BZY-QT-H group(all P<0.05).Compared with the control group,the offspring in the GDM group had higher levels of fasting blood glucose,AUC,FINS,HOMA-IR,GHb,TG,TC and LDL,and lower levels of ISI and HDL(all P<0.05);com-pared with the GDM group,the levels of fasting blood glucose,AUC,FINS,HOMA-IR,GHb,TG,TC and LDL were lower,and the levels of ISI and HDL were higher in offspring of the BZYQT-L group,BZYQT-M group and BZYQT-H group(all P<0.05).Compared with the control group,the relative expression levels of PPARGC1 A mRNA and protein in the pancreatic tissues of the pregnant rats of the GDM group were higher,and the methylation level was lower(all P<0.05);compared with the GDM group,the relative expression levels of PPARGC1 A mRNA and protein in pancreatic tis-sue of pregnant rats in the BZYQT-L group,BZYQT-M group and BZYQT-H group were lower,and the methylation level was higher(all P<0.05).Conclusions Buzhong Yiqi decoction has a good effect on GDM in pregnant rats,which can effectively improve the glucose metabolism function of rats'offspring,and the mechanism may be that Buzhong Yiqi decoc-tion can reduce the methylation of PPARGC1 A in pancreatic tissues of GDM pregnant rats and offspring.