ABSTRACT
Aim To explore the effects of prenatal caf-feine exposure (PCE) on fetal renal growth retardation and corticosterone on the gene expression of metanephric mesenchyme stem cells.Methods Pregnant Wistar rats were administered with caffeine (30,120 mg ·kg-1) from gestational day 9 to 20.Female fetal kidney samples were collected for morphological observation and gene expression examination.The metanephric mesenchyme stem cells were harvested for cell culture,and renal related genes were detected after the treatment of corticosterone with different concentrations (250,500,1 000 μg · L-1) for 24 hours.Results Compared with the control group,the fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft,accompanied with the repression of the gene expression of glial-cell-line-derived neurotrophic factor/tyrosine kinase receptor (GDNF/c-Ret) signaling pathway.The GDNF/c-Ret signaling pathway and angiotensin Ⅱ receptor type 1 (AT1R)/AT2R expression of metanephric mesenchyme stem cells also decreased in corticosterone groups.Conclusions PCE may induce dysplasia of female fetal kidneys.The potential mechanism is related to the repression of the gene expression of AT1R/AT2R and GDNF/c-Ret signaling pathway by PCE mediated by corticosterone in utero.
ABSTRACT
Objective To investigate the effects of paeonol on renin-angiotensin system (RAS) occurred on the development of ventricular remodeling after acute myocardial infarction (AMI) in rats. Methods The left anterior descending coronary artery was ligated to establish the model of AMI in male SD rats. Six groups were set up:sham-operation group, AMI model group, captopril control group, paeonol low dose group (6 mg/kg), paeonol middle dose group (9 mg/kg) and paeonol high dose group (12 mg/kg). Rats were given treatment for 4 weeks after the AMI model was established. HE staining was used to observe changes of myocardial tissue. Real-time PCR was used to detect the mRNA levels of angiotensinogen (AGT), angiotensin Ⅱ receptor type1(AGTR1) and endothelin (ET)-1 of six groups. Western blot assay was used to detect the protein levels of peptidyl-dipeptidase A (ACE), angiotensin Ⅱ(Ang)-Ⅱand AGTR1 in six groups. Results The transcription of AGT, AGTR1, ET-1mRNA and the expressions of ACE, Ang-Ⅱ and AGTR1 protein were significantly higher in myocardial tissue of AMI rats than those of sham-operation rats (P＜0.05). Compared with model group, the expressions of AGT, AGTR1, ET-1mRNA and ACE, Ang-Ⅱ, AGTR1 protein were significantly decreased in paeonol high dose group and captopril control group (P＜0.05). Paeonol reduced the expressions of those mRNA and protein levels in a significant dose dependent manner. Conclusion Paeonol can slow down the deterioration of the ventricular remodeling after AMI in rats, which may be related to the inhibition of over-activation of RAS.