ABSTRACT
Objective To explore the effect of exercise on vascular smooth muscle cell(VSMC) phenotype switching in hypertensive arteries and to figure out the regulatory mechanisms of mircroRNA (miR)-143/145 on Akt signaling during the process.Methods Three-month old(Wistar Kyoto rats) WKY and (spontaneously hypertensive rats) SHR were divided into 4 groups:WKY-C,SHR-C,WKY-E,and SHR-E,which were subjected to 8wk moderate treadmill training (E) or sedentary as control (C) with blood pressure being monitored.After the last bout of exercise,mesenteric arteries were isolated to determine VSMC phenotypic marker,miR143/145 expression and Akt phosphorylation.In transfection experiment in vitro,miR-145 mimic and miR-145 inhibitor were transfected into cultured VSMC,and given immunofluorescent staining using α-actin to detect the cell morphology.VSMC phenotype marker,Akt phosphorylation,and mRNA expressions of the insulin-like growth factor Ⅰ receptor (IGF-IR),Insulin receptor substrate 1 antibody(IRS-1),and p70S6K were determined.Results The blood pressure of SHR-E reduced significantly compared with that of SHR-C(P＜0.05),and the arterial thicknessof SHR-E decreased significantly (P＜0.05).The VSMC contractile marker calponin in SHR-E increased significantly when compared with SHR-C(P＜0.05),while the proliferative marker osteoppontin (OPN) in SHR-E reduced significantly than that in SHR-C(P＜0.05).The miR-145 of SHR-E was significantly enhanced(P＜0.05),while there was no significant difference in the miR-143.The Akt of SHR-E was activated more significantly than SHR-C(P＜0.05).The miR-145 overexpression by transfecting miR-145 mimic into VSMC increased α-actin significantly(P＜0.05),while miR-145 inhibitor made α-actin a decrease.Akt activation was significantly inhibited by miR-145 mimic and enhanced by miR-145 inhibitor(P＜0.05).The miR-145 significantly inhibited IRS-1 and IGF-1R mRNA(P＜ 0.05),but the targeting effects were not significant on p70S6K mRNA.Conclusions Exercise ameliorates the high blood pressure and remodels arterioles,which may rely on its regulatory role on VSMC switching from proliferative to contractile phenotype,and miR-145 is involved in this process.However,the Akt activation is not caused by the overexpression of miR-145,but through other means to promote the above VSMC switching.
ABSTRACT
ObjectiveTo search clinical operational threshold of neonatal hypoglycemia.Methods From Jan 2007 to Jan 2009,128 neonates in our hospital were divided into 4 groups:normal control group (blood glucose range 3.30 ～ 6.10 mmol/L during hospitalization) ;treatment I group (blood glucose range 2.60 ～ 3.29 mmol/L keep 2 h,maintain normal range after 4 h) ; treatment Ⅱ group ( blood glucose range 2.20 ～ 2.59 mmol/L keep 2 h,maintain normal range after 4 h ) ;treatment Ⅲ group(blood glucose ＜2.20 mmol/L keep 2 h,maintain normal range after 3 h).Relevant data of the latency of main waves on the neonates were collected and analyzed by flash visual evoked potential( F-VEP) test.ResultsThe main waves of F-VEP in all the 128 neonates were existed.The latency of main waves in group Ⅱ [ (212.9 ± 18.9) ms] and group Ⅲ [ (223.1 ±20.4) ms] were significantly longer than that in the normal control group [ ( 199.2 ± 14.3) ms] respectively (P ＜0.01 ),and the latency of main wavesin group Ⅲ were longer than that in group Ⅱ ( P ＜0.01 ).There were no significant difference in group I [ (203.3 ± 15.4) ms ] as compared with the other groups (P ＞ 0.05 ).When blood glucose of the treatment group maintain on 3.30 ～ 6.10 mmol/L,the latency of main waves of F-VEP in group Ⅱ and group Ⅲ [ (202.9 ± 15.2) ms,(203.1 ± 15.5) ms ] had no differences as compared with the control group[ ( 199.2 ± 14.3 ) ms ] (P ＞ 0.05 ).ConclusionIt may be appropriate that the threshold of blood glucose for diagnostic criteria of neonatal hypoglycemia is less than 2.60 mmol/L rather than 2.20 mmol/L,whether the neonates have any clinical manifestations or not.