Objective:To explore the function and mechanism of microRNA-155 to regulate the angiogenesis after the cerebral infarction of rats through the angiotensin Ⅱ receptor 1(AT1R)/vascular endothelial growth factor(VEGF) s...Objective:To explore the function and mechanism of microRNA-155 to regulate the angiogenesis after the cerebral infarction of rats through the angiotensin Ⅱ receptor 1(AT1R)/vascular endothelial growth factor(VEGF) signaling pathway.Methods:Female SD rats were chosen for the construction of cerebral infarction model of rats using the modified right middle cerebral artery occlusion.The real-time PCR(RT-PCR) method was employed to detect the expression of microRNA-155 in each group at different time points after the cerebral infarction(1 h,I d,3 d and 7 d).SD rats were randomly divided into four groups(n=20 rats):sham operation group(Sham group),MACO group,MACO+microRNA-155 mimic group,and MACO+microRNA-155 inhibitor group.Sham group was given the free graft,while MACO+microRNA-155 mimic group and MACO+microRNA-155 inhibitor group were treated with microRNA-155 mimic and microRNA-155 inhibitor respectively.The Zea Longa5-point scale was used to score the neurologic impairment of rats in each group;2,3,5-triphenyl tetrazolium chloride staining to evaluate the volume of cerebral infarction of rats in each group;the immunohistochemistry to detect the expression of CD31;Western blot and RT-PCR to detect the expression of AT1 R and VEGF receptor 2(VEGFR2).Results:The expression of microRNA-155 was increased in the cerebral ischemia tissue after the cerebral infarction.It was significantly increased at 1 d of ischemia and maintained at the high level for a long time.Rats in the Sham group had no symptom of neurologic impairment while rats in the MACO group had the obvious neurologic impairment.After being treated with microRNA-155 inhibitor,the neural function of MACO rats had been improved,with the decreased area of cerebral infarction.But after being treated with microRNA-155 mimic,the neural function was further worsened,with the increased area of cerebral infarction.Results of immunohistoehemical assay indicated that microRNA-155 inhibitor could up-regulate the expression of CD31,while microRNA-155 mimic could down展开更多
To investigate the molecular mechanism by which Tanshinone Ⅱ A （TSN Ⅱ A） prevents left ventricular hypertrophy （LVH）, we examined the expression of AT1R, TGF-β1 and Smads gene in the hypertrophic myocardium of ...To investigate the molecular mechanism by which Tanshinone Ⅱ A （TSN Ⅱ A） prevents left ventricular hypertrophy （LVH）, we examined the expression of AT1R, TGF-β1 and Smads gene in the hypertrophic myocardium of hypertensive rats with abdominal aorta constriction. LVH model was established by creating abdominal aorta constriction. Four weeks later, animals were randomly divided into 4 groups with 8 animals in each. One group was used as model control, the other three groups were treated with TSN ⅡA （20 mg/kg）, TSN ⅡA （10 mg/kg） and valsartan （10 mg/kg）, respectively. Another 8 SD rats were subjected to sham surgery and served as blank control. After 8- week treatment, the caudal artery pressure of the animals was measured. The tissues of left ventricle were taken for the measurement of the left ventricular mass index （LVMI） and pathological sectioning and HE-staining were used for determining the myocardial fiber dimension （MFD）. The mRNA expression of AT1R, protein expression of TGF-betal and activity of Smad-2, 4, 7 were detected by RT-PCR and Western blotting, respectively. Our results showed that （1） the blood pressure of rats treated with TSN Ⅱ A, either at high or low dose, was significantly higher than those in the control and valsartan-treated group （P〈0.01, P〈0.05）; （2） LVMI and MFD in TSN Ⅱ A and valsartan-treated rats were higher than those in the control group （P〈0.05） but significantly lower than those in the model control （P〈0.01）; （3） the high doses of TSN Ⅱ A and valsartan significantly down-regulated the mRNA expression of AT 1R and protein expression of TGF-beta l and Smad-3 in the hypertrophic myocardium （P〈0.01）, and TGF-betal in valsartan-treated animals was more significantly lower than that in rats treated with TSN Ⅱ A; （4） the two doses of TSN Ⅱ A and valsartan significantly up-regulated the protein expression of Smad-7 in the hypertrophic myocardium （P〈0.01）, and Smad-7 in the animals treated with展开更多
基金supported by Shandong Key Scientific and Technological Project Fund(No.2013YD 18021)
文摘Objective:To explore the function and mechanism of microRNA-155 to regulate the angiogenesis after the cerebral infarction of rats through the angiotensin Ⅱ receptor 1(AT1R)/vascular endothelial growth factor(VEGF) signaling pathway.Methods:Female SD rats were chosen for the construction of cerebral infarction model of rats using the modified right middle cerebral artery occlusion.The real-time PCR(RT-PCR) method was employed to detect the expression of microRNA-155 in each group at different time points after the cerebral infarction(1 h,I d,3 d and 7 d).SD rats were randomly divided into four groups(n=20 rats):sham operation group(Sham group),MACO group,MACO+microRNA-155 mimic group,and MACO+microRNA-155 inhibitor group.Sham group was given the free graft,while MACO+microRNA-155 mimic group and MACO+microRNA-155 inhibitor group were treated with microRNA-155 mimic and microRNA-155 inhibitor respectively.The Zea Longa5-point scale was used to score the neurologic impairment of rats in each group;2,3,5-triphenyl tetrazolium chloride staining to evaluate the volume of cerebral infarction of rats in each group;the immunohistochemistry to detect the expression of CD31;Western blot and RT-PCR to detect the expression of AT1 R and VEGF receptor 2(VEGFR2).Results:The expression of microRNA-155 was increased in the cerebral ischemia tissue after the cerebral infarction.It was significantly increased at 1 d of ischemia and maintained at the high level for a long time.Rats in the Sham group had no symptom of neurologic impairment while rats in the MACO group had the obvious neurologic impairment.After being treated with microRNA-155 inhibitor,the neural function of MACO rats had been improved,with the decreased area of cerebral infarction.But after being treated with microRNA-155 mimic,the neural function was further worsened,with the increased area of cerebral infarction.Results of immunohistoehemical assay indicated that microRNA-155 inhibitor could up-regulate the expression of CD31,while microRNA-155 mimic could down
基金supported by a grant from the National Natural Science Foundation of China(No.30500657)
文摘To investigate the molecular mechanism by which Tanshinone Ⅱ A （TSN Ⅱ A） prevents left ventricular hypertrophy （LVH）, we examined the expression of AT1R, TGF-β1 and Smads gene in the hypertrophic myocardium of hypertensive rats with abdominal aorta constriction. LVH model was established by creating abdominal aorta constriction. Four weeks later, animals were randomly divided into 4 groups with 8 animals in each. One group was used as model control, the other three groups were treated with TSN ⅡA （20 mg/kg）, TSN ⅡA （10 mg/kg） and valsartan （10 mg/kg）, respectively. Another 8 SD rats were subjected to sham surgery and served as blank control. After 8- week treatment, the caudal artery pressure of the animals was measured. The tissues of left ventricle were taken for the measurement of the left ventricular mass index （LVMI） and pathological sectioning and HE-staining were used for determining the myocardial fiber dimension （MFD）. The mRNA expression of AT1R, protein expression of TGF-betal and activity of Smad-2, 4, 7 were detected by RT-PCR and Western blotting, respectively. Our results showed that （1） the blood pressure of rats treated with TSN Ⅱ A, either at high or low dose, was significantly higher than those in the control and valsartan-treated group （P〈0.01, P〈0.05）; （2） LVMI and MFD in TSN Ⅱ A and valsartan-treated rats were higher than those in the control group （P〈0.05） but significantly lower than those in the model control （P〈0.01）; （3） the high doses of TSN Ⅱ A and valsartan significantly down-regulated the mRNA expression of AT 1R and protein expression of TGF-beta l and Smad-3 in the hypertrophic myocardium （P〈0.01）, and TGF-betal in valsartan-treated animals was more significantly lower than that in rats treated with TSN Ⅱ A; （4） the two doses of TSN Ⅱ A and valsartan significantly up-regulated the protein expression of Smad-7 in the hypertrophic myocardium （P〈0.01）, and Smad-7 in the animals treated with
