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The Cardiac Toxicity And Glycyrrhizin Protective Effect Of Mother And Offspring Rats In Pregnant Female Rats Exposed To HAART Drugs

Posted on:2021-02-19Degree:MasterType:Thesis
Country:ChinaCandidate:Z S ChenFull Text:PDF
GTID:2504306128967999Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
Objective: An experimental model of HAART drug exposure and glycyrrhizin intervention in the gestation period of female rats was prepared to observe the effect of HAART drug exposure on the heart of mother and offspring and the protective effect of glycyrrhizin during the gestation period of female rats.Method: Nine 10-week-old SD clean grade male rats and 27 female rats were randomly divided into 3 groups: control group(CON group),HAART drug exposure group(HAART group),and glycyrrhizin intervention group(HAART + GL group).Three male rats and nine female rats were fed in a cage in each group,and the female rats were gavaged twice a day.Female rats in the CON group were given saline(NS,10 ml / Kg)each time,and female rats in the HAART group were given equal volume HAART drugs(LPV / r(41.67 / 10.42)mg / kg + 3TC 15.63 mg / kg + AZT 31.25 mg / kg),The HAART + GL group was given an equal volume of HAART drug + glycyrrhizin(100 mg / kg)until the offspring were born and their body weight increased to 100 g.The male and female offspring are reared in cages until they weigh 200 g.Mother and son rats undergo cardiac echocardiography for left ventricular end-diastolic diameter(LVDd),ventricular septal thickness(IVST),left ventricular posterior wall thickness(LVPWT),aortic sinus(AOD),left atrial inner diameter(LA),Blood fraction(EF),carotid blood pressure(HR,SP,DP,PP,m AP),left ventricular hemodynamic indicators(HR,LVSP,LVDP,LVP ± dp / dtmax);Abdominal aorta blood sampling for biochemistry Indicators: Glucose(GLU),blood lipids(LDL-C,TG,TC and HDL-C),serum myocardial enzymes AST,ALT,CK,LDH,take myocardial tissue to measure ALT,AST,Na +-K +-ATP Enzyme;HE staining to observe the myocardial histological structure,Masson staining to observe the myocardial tissue fibrosis,and transmission electron microscopy to observe the ultrastructure of myocardial cells.Results: Compared with the CON group,the body weight of the HAART group showed a declining change(P <0.05);cardiac ultrasound showed large LVDd(P <0.05),IVST thickness(P <0.01),LVPWT thickness(P <0.05),LA Large(P <0.05);DP high(P <0.05);LVP + dp / dtmax decreased(P <0.01);blood GLU high,TG low(P <0.05),AST low(P <0.05),CK low(P <0.01);myocardial tissue ALT is low(P <0.05);HE staining shows abnormal myocardial histological structure;Masson staining shows myocardial collagen fiber hyperplasia;transmission electron microscopy shows myocardial cell ultrastructure abnormality.Compared with the HAART group,the weight of the mother mice in the HAART + GL group remained stable;SP,DP,MBP,and HR were low(P <0.01),no difference from the CON group(P> 0.05);LVP-dp / dtmax was low(P> 0.05);low blood GLU(P> 0.05),no difference from the CON group(P> 0.05),high LDL(P <0.05);high HDL and T-cho(P <0.05),higher than the CON group(P <0.05)0.01);CK is high(P <0.05),no difference from the CON group(P> 0.05);LDH is high(P> 0.05),higher than the CON group(P <0.05);HE staining shows no obvious abnormality in myocardial histology There is no obvious collagen fiber in Masson staining of myocardial tissue;there is no obvious abnormality in the ultrastructure of myocardial cells detected by transmission electron microscopy.Compared with the CON group,the HAART group had lower birth weight(P <0.01),no difference on the 15 th day(P> 0.05),and overweight on the 43 rd day(P <0.01).3-month-old male offsprings have large AOD(P <0.05);high DP(P <0.05)and high HR(P <0.01);high LVSP,low LVP-dp / dtmax(P <0.01);low blood LDL and HDL(P <0.05);low ALT in myocardial tissue(P <0.05);collagen fiber hyperplasia in myocardial tissue.LVDd(P <0.05),LV(P <0.01)decreased,ventricular muscle hypertrophy in 3-month-old female offspring;SP,DP,MBP,HR were high(P <0.01),and pulse pressure difference was low(P <0.01);High(P <0.05),fast HR(P <0.05),high LVP + dp / dtmax(P <0.05);high blood LDL(P <0.05),low CK,LDH(P <0.05),HE staining see myocardium Abnormal histological structure;Masson staining showed increased collagen fibers in myocardial tissue.Compared with the HAART group,the HAART + GL group had lower birth weight(P <0.05),and there was no difference between the CON group and the CON group on the 43 rd day(P> 0.05);Low EF(P <0.01),E peak decreased(P <0.01);DP,MBP,pulse pressure difference(P <0.01),no difference from the CON group(P> 0.05);LVSP was low(P <0.05),LVP-dp / dtmax is lower than that in the CON group(P <0.05);TG(P <0.01)is low;LDL is high(P <0.05),no difference from the CON group(P> 0.05);HDL is lower than the CON group(P <0.01);AST is high(P <0.05),no difference from the CON group;Na +-K +-ATPase activity is higher than the CON group(P <0.05);ALT is lower than the CON group(P <0.05);HE staining shows myocardium There was no obvious abnormality in the histological structure;there was no obvious collagen fiber in Masson staining.The 3-month-old female sons’ ultrasound showed that AOD was small(P <0.05);SP,DP,MBP and HR were low(P <0.01),no difference from the CON group(P> 0.05);LVEDP was high(P <0.05)Low LDL,no difference with the CON group(P> 0.05);CK and LDH were high(P <0.05),no difference with the CON group(P> 0.05);Myocardial tissue ALT was high(P <0.05),higher than CON Group(P <0.05);HE staining showed no obvious abnormality in myocardial histological structure;Masson staining showed no obvious collagen fibers.Conclusion: 1.Female rats are given intragastric administration of HAART medicine(LPV / r + 3TC + AZT)once a day until the weight of the offspring reaches 100 grams.Experimental model of HAART drug exposure.2.The exposure of HAART drugs during the gestation period of female rats caused abnormal growth,metabolism,cardiovascular structure and function of mother and offspring.Compared with male rats,female rats have more obvious cardiovascular structure and function abnormalities.3.Glycyrrhizin(100mg / Kg,bid)can protect mother and offspring exposed to HAART drugs during pregnancy,prevent toxic damage of HAART drugs,and maintain normal growth,metabolism,cardiovascular function and structure of mother and offspring.
Keywords/Search Tags:Myocardial protection, HIV mother-to-child block, Zidovudine(AZT), Lamivudine(3TC), Kelizhi(LPV/r), Glycyrrhizin
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