Angiotension-Ⅱ(A-Ⅱ) receptor maximal binding capacity (Bmax) and dissociation constants (Kd) of different blood vessels in rats with prehepatic portal hypertension were studied by radioligand binding analysis. The r...Angiotension-Ⅱ(A-Ⅱ) receptor maximal binding capacity (Bmax) and dissociation constants (Kd) of different blood vessels in rats with prehepatic portal hypertension were studied by radioligand binding analysis. The results showed that the A-Ⅱreceptor Bmax. in the thoracic aorta, superior mesenteric artery and portal vein of portal hypertensive animals (113. 7±19. 4 fmol/mg protein, 206.9 ±39. 3 fmol/mg protein and 31. 5±9. 2 fmol/mg protein respectively ) was all significantly lower than that of controls (146. 8±24. 5 fmol/mg protein, 297. 2±44. 7 fmol/mg protein and 53. 4±12.1 fmol/mg protein respectively, P＜0. 01).The A-Ⅱ receptor Kd in the superior mesenteric artery was markedly increased in portal hypertensive animals (1. 03±0.11 nmol/L) compared with that in controls (0. 88±0. 08 nmol/L, P＜0. 05). In the thoracic aorta and portal vein, the A-Ⅱ receptor Kd in portal hypertensive animals was slightly higher than that in controls, but no significant difference was observed between the two groups. The results suggested that the vascular hyporesponsiveness to A-Ⅱ in portal hypertension was caused partially by a reduction in number and a decrease in affinity of vascular A- Ⅱ receptors, and these changes might possibly lead to the formation of hyperdynamic circulation.展开更多
Angiotensin Ⅱ (ANGⅡ) plays an important role in the pathogenesis of atherosclerosis by inducing proliferation of vascular smooth muscle cells (VSMCs).In our study,we observed the effects of valsartan on proliferatio...Angiotensin Ⅱ (ANGⅡ) plays an important role in the pathogenesis of atherosclerosis by inducing proliferation of vascular smooth muscle cells (VSMCs).In our study,we observed the effects of valsartan on proliferation of cultured VSMCs treated with or without ANGⅡ by cell counting and methyl thiazolyl tetrazolium (MTT) assay,and detected the expression of mitofusin 2 (Mfn2),a newly discovered cell proliferation inhibitor and a related cell proliferation signaling pathway pro-tein by Western blotting.ANGⅡ at a concentration of 10-6 mol/L significantly stimulated VSMCs proliferation,down-regulated the expression of Mfn2 and upregulated the expression of Raf and ERK1/2.Valsartan inhibited such effects of ANGⅡ at concentrations of 10-5 and 10-6 mol/L,but not at 10-7 mol/L.Valsartan had no significant effect on the proliferation of untreated VSMCs.These results suggest that valsartan inhibits ANGⅡ-induced proliferation of VSMCs in vitro via Mfn2-Ras-Raf-ERK/MAPK signaling pathway.展开更多
Angiotensin Ⅱ(Ang Ⅱ), an endogenous peptide hormone, plays critical roles in the pathophysiological modulation of cardiovascular functions. Ang Ⅱ is the principle effector of the renin-angiotensin system for mainta...Angiotensin Ⅱ(Ang Ⅱ), an endogenous peptide hormone, plays critical roles in the pathophysiological modulation of cardiovascular functions. Ang Ⅱ is the principle effector of the renin-angiotensin system for maintaining homeostasis in the cardiovascular system, as well as a potent stimulator of NAD(P)H oxidase, which is the major source and primary trigger for reactive oxygen species(ROS) generation in various tissues. Recent accumulating evidence has demonstrated the importance of oxidative stress in Ang Ⅱ-induced heart diseases. Here, we review the recent progress in the study on oxidative stress-mediated effects of Ang Ⅱ in the cardiovascular system. In particular, the involvement of Ang Ⅱ-induced ROS generation in arrhythmias, cell death/heart failure, ischemia/reperfusion injury, cardiac hypertrophy and hypertension are discussed. Ca2+/calmodulin-dependent protein kinase Ⅱ is an important molecule linking Ang Ⅱ, ROS and cardiovascular pathological conditions.展开更多
Previous work from this laboratory has demonstrated that the addition of angiotensin(Aug)Ⅱresults in the rapid transcriptional activation of early growth response gene c-fos.Blockage of this increase completely inhib...Previous work from this laboratory has demonstrated that the addition of angiotensin(Aug)Ⅱresults in the rapid transcriptional activation of early growth response gene c-fos.Blockage of this increase completely inhibits the Aug Ⅱinduced increase in vascular smooth muscle cell(VSMC)growth.To explore the molecular mechanism responsible for the induction of c-fos in VSMC,a series of constructs containing portions of c-fos promoter linked to the reporter gene chloramphenicol acetyltransferase(CAT)were used in transient transfection assays.When a construct containing both the well described serum response element(SRE)and the cyclic AMP response element(CRE)was used,no endogenous CAT activity was observed in serum starved cells.The addition of either Ang Ⅱor serum resulted in a marked increase in CAT activity.Mutations in either the SRE or CRE alone which have been demonstrated to inactivate these elements in number of cell types had no effect on c-fos inducibility by either Angll or serum. In contrast,if both elements were mutated in the same construct,inducibility was reduced by 75 %￣80%.Using a construct in which the SRE has been deleted,a mutation in the CRE completely abolished induction of c-fos by either Aug Ⅱor serum. Mobility shift assays demonstrated that tow proteins bind specifically to the SRE and three proteins to CRE. These data demonstrate that the induction of c-fos in VSMC's can be mediated by two distinct enhancer elements each of which can act independently. Future research will be aimed at identifying the proteins that interact with these elemetns delineating the mechanisms by which Ang Ⅱstimulates their activity.展开更多
Objective: To study the relationship between the activity changes of angiotensin II (Ang II ) in plasma, cerebrospinal fluid (CSF) and the pathophysiology of vascular dementia (VD) on the one hand and the therapeutic ...Objective: To study the relationship between the activity changes of angiotensin II (Ang II ) in plasma, cerebrospinal fluid (CSF) and the pathophysiology of vascular dementia (VD) on the one hand and the therapeutic effects of ligustrazine (LIG) on VD and its mechanisms on the other hand. Methods: Case grouping: VD group with 50 cases (26 VD patients treated with LIG and 24 with Ginaton) ; cerebral infarction (CI) group with 62 cases (routine therapy was given) and control group (without organic disease in central nervous system) with 26 cases. Investigation method ? To test cognitive function by Mini-Mental State Examination (MMSE), Functional Activities Questionnaire (FAQ), Hachinski Ischemic Scale (HIS) and P300 peak latency (P300PL) . To measure the concentration of AngII by radioimmunoassay (RIA) technology. Results: As compared with CI recovery phase or with control group, AngII levels in CSF were markedly increased in VD group(P<0. 01), MMSE scores was significantly lowered (P<0. 01), P300PL was markedly prolonged (P<0 01) . In VD group, after treatment with LIG or Ginaton, levels of AngII in plasma or CSF were markedly lowered (P<0. 01) . The MMSE scores was significantly increased (P<0.05), P300PL was markedly shortened (P<0.01) . After treatment, no significant difference was found between LIG and Ginaton therapeutic subgroups (P>0.05) . Conclusion: AngII activity changes plays an important role in pathophysiological process of VD. LIG can improve cognitive function in VD. It may be correlated with improving of the disorders of Ang II in central nervous system.展开更多
Objective： Interleukin-8（IL-8） represents the prototypical chemokine that is made by a wide variety of cell types. Previously studies have suggested that angiotensin Ⅱ（Ang Ⅱ） is involved in atherogenesis throug...Objective： Interleukin-8（IL-8） represents the prototypical chemokine that is made by a wide variety of cell types. Previously studies have suggested that angiotensin Ⅱ（Ang Ⅱ） is involved in atherogenesis through induction ofproinflammatory cytokines such as interleukin- 6 or monocyte chemoattractant protein-1（MCP-1） in vascular smooth muscle cells（VSMCs）, while the role of Ang II on IL-8 expression in VSMCs is poorly studied. Methods： In this study, VSMCs were isolated from the thoracic aorta of Sprague-Dawley rats. The expression of smooth muscle α-actin was confirmed by an immunohistochemical method. Semi-quantitative RT-PCR and enzyme-linked immunosorbent assay （ELISA） analyses were conducted to detect IL-8 expression. Results： In the present study we found that Ang Ⅱ significantly increased the expression of IL-8 both at the mRNA and protein levels in rat VSMCs in a dose- and time-dependent manner. Conclusion： These findings suggested that Ang Ⅱ may participate in atherosclerosis through induction of inflammatory mediator in VSMCs.展开更多
Functional responses to angiotensin Ⅱ (AT-Ⅱ) were determined in aortic vascular smooth muscle cells (VSMCs) from experimental cirrhotic rats. Our data showed that AT-Ⅱ-stimulated extracellular acidification rate (E...Functional responses to angiotensin Ⅱ (AT-Ⅱ) were determined in aortic vascular smooth muscle cells (VSMCs) from experimental cirrhotic rats. Our data showed that AT-Ⅱ-stimulated extracellular acidification rate (ECAR), which was measured by Cytosensor microphysiometry, was significantly reduced in the aortic VSMCs from the cirrhotic rats as compared to those from the control animals. The ability of AT-Ⅱ to promote formation of inositol phosphates, the second messenger produced by the activation of Gq-coupled receptors, was also considerably suppressed in the cirrhotic VSMCs. Furthermore, the maximal p42/44 MAPK phosphorylation stimulated by AT-Ⅱ was significantly reduced in the cirrhotic VSMCs in contrast to that in the normal VSMCs. Taken together, our data clearly demonstrated that the functional responses to AT-Ⅱ was severely suppressed in aortic VSMCs in cirrhosis, indicating the impairment of general Gq-coupled receptor signaling and subsequent biological function in the cirrhotic VSMCs.展开更多
Angiotensin Ⅱ immunoreactivity (ir-Ang Ⅱ) was measured in brain areas,known to be involved in the control of circulation, in spontaneously hypertensive rats(SHR) and normotensive, Wistar Kyoto rats as controls (WKY...Angiotensin Ⅱ immunoreactivity (ir-Ang Ⅱ) was measured in brain areas,known to be involved in the control of circulation, in spontaneously hypertensive rats(SHR) and normotensive, Wistar Kyoto rats as controls (WKY) of 1-]2 weeks old and of both sexes. The systolic pressure (SP), in rats of 4-12 weeks old,increased with age and was signifficantly higher in SHR than WKY. In SHR, the increase was also significantly greater in male than female. The ir-Ang Ⅱ increased with age in all cardiovascular brain areas up to 12 weeks old in SHR, but only up to 4 weeks old in WKY. There was also sex difference in SHR. The changes in ir-Ang Ⅱ, particularly in the ventrolateral medulla (VLM), correlated well with changes in SP. The findings suggest thal interaction between brain Ang Ⅱ and cardiovascular brain areas, particularly the VLM and hypothalamus, may be crucial in the development of hypertension. The results also indicale sexual dimorphism in brain Ang Ⅱ in addition to blood pressure reaction in the developing SHR.展开更多
To investigate the effects of icariin （ICA） on angiotensin Ⅱ（Ang Ⅱ）-induced injury in human umbilical vein endothelial cells line （ECV-304）. The ECV-304 cells were cultured in vitro. After 24 h incubating with...To investigate the effects of icariin （ICA） on angiotensin Ⅱ（Ang Ⅱ）-induced injury in human umbilical vein endothelial cells line （ECV-304）. The ECV-304 cells were cultured in vitro. After 24 h incubating with icariin, the model of AngⅡ-induced injury in ECV-304 was established. The cell viability （MTT method）, Lactate dehydrogenase （LDH） release and Nitric oxide （NO） production in the medium, the capacity of scavenging superoxide anion radicals （O2^-） and hydroxyl radicals （.OH） were measured. The activities of superoxide dismutase （SOD）, total nitric oxide synthase （T-NOS）, inducible nitric oxide synthase （iNOS） and constitutive nitric oxide synthase （cNOS） in the cells were determined. Compared with the Ang Ⅱ-treated group, ICA can significantly raise the viability of EC, increase the activities of SOD, T-NOS and cNOS, increase the production of NO, enhance the capacity of scavenging superoxide anion radicals （ O2^- ） and hydroxyl radicals（.OH）, and lower LDH leakage and iNOS activity. The results suggest that ICA can protect endothelial cells （ECV-304） from Ang II-induced injury.展开更多
The changes of proto-oncogene c-fos and c-jun mRNA expression in angiotensin Ⅱ （AngⅡ）-induced hypertrophy and effects of sodium tanshinone ⅡA sulfonate （STS） in the primary culture of neonatal rat cardiomyocyte...The changes of proto-oncogene c-fos and c-jun mRNA expression in angiotensin Ⅱ （AngⅡ）-induced hypertrophy and effects of sodium tanshinone ⅡA sulfonate （STS） in the primary culture of neonatal rat cardiomyocytes were investigated. Twelve neonatal clean grade Wistar rats were selected. The cardiomyocytes were isolated, cultured and divided according to different treatments in the medium. The cardiomyocyte size was determined by phase contrast microscope, and the rate of protein synthesis was measured by [3H]-Leucine incorporation. The c-fos and c-jun mRNA expression in cardiomyocytes was detected by reverse transcription polymerase chain reaction （RT-PCR）. It was found after cardiomyocytes were treated with AngⅡ for 30 min, the c-fos and c-jun mRNA expression in cardiomyocytes was increased significantly （P〈0.01）. After treatment with AngⅡ for 24 h, the rate of protein synthesis in AngⅡ group was significantly increased as compared with control group （P〈0.01）. After treatment with AngⅡ for 7 days, the size of cardiomyocytes in AngⅡ group was increased obviously as compared with control group （P〈0.05）. After pretreatment with STS or Valsartan before AngⅡ treatment, both of them could inhibit the above effects of AngⅡ （P〈0.05 or P〈0.01）. It was suggested that STS could ameliorate AngⅡ-induced cardiomyocyte hy- pertrophy by inhibiting c-fos and c-jun mRNA expression and reducing protein synthesis rate of cardiomyocytes.展开更多
文摘Angiotension-Ⅱ(A-Ⅱ) receptor maximal binding capacity (Bmax) and dissociation constants (Kd) of different blood vessels in rats with prehepatic portal hypertension were studied by radioligand binding analysis. The results showed that the A-Ⅱreceptor Bmax. in the thoracic aorta, superior mesenteric artery and portal vein of portal hypertensive animals (113. 7±19. 4 fmol/mg protein, 206.9 ±39. 3 fmol/mg protein and 31. 5±9. 2 fmol/mg protein respectively ) was all significantly lower than that of controls (146. 8±24. 5 fmol/mg protein, 297. 2±44. 7 fmol/mg protein and 53. 4±12.1 fmol/mg protein respectively, P＜0. 01).The A-Ⅱ receptor Kd in the superior mesenteric artery was markedly increased in portal hypertensive animals (1. 03±0.11 nmol/L) compared with that in controls (0. 88±0. 08 nmol/L, P＜0. 05). In the thoracic aorta and portal vein, the A-Ⅱ receptor Kd in portal hypertensive animals was slightly higher than that in controls, but no significant difference was observed between the two groups. The results suggested that the vascular hyporesponsiveness to A-Ⅱ in portal hypertension was caused partially by a reduction in number and a decrease in affinity of vascular A- Ⅱ receptors, and these changes might possibly lead to the formation of hyperdynamic circulation.
基金supported by grants from the National Natural Science Foundation of China (No. 30872714 and No.30971244)
文摘Angiotensin Ⅱ (ANGⅡ) plays an important role in the pathogenesis of atherosclerosis by inducing proliferation of vascular smooth muscle cells (VSMCs).In our study,we observed the effects of valsartan on proliferation of cultured VSMCs treated with or without ANGⅡ by cell counting and methyl thiazolyl tetrazolium (MTT) assay,and detected the expression of mitofusin 2 (Mfn2),a newly discovered cell proliferation inhibitor and a related cell proliferation signaling pathway pro-tein by Western blotting.ANGⅡ at a concentration of 10-6 mol/L significantly stimulated VSMCs proliferation,down-regulated the expression of Mfn2 and upregulated the expression of Raf and ERK1/2.Valsartan inhibited such effects of ANGⅡ at concentrations of 10-5 and 10-6 mol/L,but not at 10-7 mol/L.Valsartan had no significant effect on the proliferation of untreated VSMCs.These results suggest that valsartan inhibits ANGⅡ-induced proliferation of VSMCs in vitro via Mfn2-Ras-Raf-ERK/MAPK signaling pathway.
基金Supported by A NIH R01 Grant,No.HL097979(to Xie LH)
文摘Angiotensin Ⅱ(Ang Ⅱ), an endogenous peptide hormone, plays critical roles in the pathophysiological modulation of cardiovascular functions. Ang Ⅱ is the principle effector of the renin-angiotensin system for maintaining homeostasis in the cardiovascular system, as well as a potent stimulator of NAD(P)H oxidase, which is the major source and primary trigger for reactive oxygen species(ROS) generation in various tissues. Recent accumulating evidence has demonstrated the importance of oxidative stress in Ang Ⅱ-induced heart diseases. Here, we review the recent progress in the study on oxidative stress-mediated effects of Ang Ⅱ in the cardiovascular system. In particular, the involvement of Ang Ⅱ-induced ROS generation in arrhythmias, cell death/heart failure, ischemia/reperfusion injury, cardiac hypertrophy and hypertension are discussed. Ca2+/calmodulin-dependent protein kinase Ⅱ is an important molecule linking Ang Ⅱ, ROS and cardiovascular pathological conditions.
文摘Previous work from this laboratory has demonstrated that the addition of angiotensin(Aug)Ⅱresults in the rapid transcriptional activation of early growth response gene c-fos.Blockage of this increase completely inhibits the Aug Ⅱinduced increase in vascular smooth muscle cell(VSMC)growth.To explore the molecular mechanism responsible for the induction of c-fos in VSMC,a series of constructs containing portions of c-fos promoter linked to the reporter gene chloramphenicol acetyltransferase(CAT)were used in transient transfection assays.When a construct containing both the well described serum response element(SRE)and the cyclic AMP response element(CRE)was used,no endogenous CAT activity was observed in serum starved cells.The addition of either Ang Ⅱor serum resulted in a marked increase in CAT activity.Mutations in either the SRE or CRE alone which have been demonstrated to inactivate these elements in number of cell types had no effect on c-fos inducibility by either Angll or serum. In contrast,if both elements were mutated in the same construct,inducibility was reduced by 75 %￣80%.Using a construct in which the SRE has been deleted,a mutation in the CRE completely abolished induction of c-fos by either Aug Ⅱor serum. Mobility shift assays demonstrated that tow proteins bind specifically to the SRE and three proteins to CRE. These data demonstrate that the induction of c-fos in VSMC's can be mediated by two distinct enhancer elements each of which can act independently. Future research will be aimed at identifying the proteins that interact with these elemetns delineating the mechanisms by which Ang Ⅱstimulates their activity.
基金Foundation item: Item provided by Commission of Science and Technology of Chongqing City(No. 5657)
文摘Objective: To study the relationship between the activity changes of angiotensin II (Ang II ) in plasma, cerebrospinal fluid (CSF) and the pathophysiology of vascular dementia (VD) on the one hand and the therapeutic effects of ligustrazine (LIG) on VD and its mechanisms on the other hand. Methods: Case grouping: VD group with 50 cases (26 VD patients treated with LIG and 24 with Ginaton) ; cerebral infarction (CI) group with 62 cases (routine therapy was given) and control group (without organic disease in central nervous system) with 26 cases. Investigation method ? To test cognitive function by Mini-Mental State Examination (MMSE), Functional Activities Questionnaire (FAQ), Hachinski Ischemic Scale (HIS) and P300 peak latency (P300PL) . To measure the concentration of AngII by radioimmunoassay (RIA) technology. Results: As compared with CI recovery phase or with control group, AngII levels in CSF were markedly increased in VD group(P<0. 01), MMSE scores was significantly lowered (P<0. 01), P300PL was markedly prolonged (P<0 01) . In VD group, after treatment with LIG or Ginaton, levels of AngII in plasma or CSF were markedly lowered (P<0. 01) . The MMSE scores was significantly increased (P<0.05), P300PL was markedly shortened (P<0.01) . After treatment, no significant difference was found between LIG and Ginaton therapeutic subgroups (P>0.05) . Conclusion: AngII activity changes plays an important role in pathophysiological process of VD. LIG can improve cognitive function in VD. It may be correlated with improving of the disorders of Ang II in central nervous system.
基金supported by the Shanghai Science and Technology Committee Grant (No.03DJ14019)
文摘Objective： Interleukin-8（IL-8） represents the prototypical chemokine that is made by a wide variety of cell types. Previously studies have suggested that angiotensin Ⅱ（Ang Ⅱ） is involved in atherogenesis through induction ofproinflammatory cytokines such as interleukin- 6 or monocyte chemoattractant protein-1（MCP-1） in vascular smooth muscle cells（VSMCs）, while the role of Ang II on IL-8 expression in VSMCs is poorly studied. Methods： In this study, VSMCs were isolated from the thoracic aorta of Sprague-Dawley rats. The expression of smooth muscle α-actin was confirmed by an immunohistochemical method. Semi-quantitative RT-PCR and enzyme-linked immunosorbent assay （ELISA） analyses were conducted to detect IL-8 expression. Results： In the present study we found that Ang Ⅱ significantly increased the expression of IL-8 both at the mRNA and protein levels in rat VSMCs in a dose- and time-dependent manner. Conclusion： These findings suggested that Ang Ⅱ may participate in atherosclerosis through induction of inflammatory mediator in VSMCs.
文摘Functional responses to angiotensin Ⅱ (AT-Ⅱ) were determined in aortic vascular smooth muscle cells (VSMCs) from experimental cirrhotic rats. Our data showed that AT-Ⅱ-stimulated extracellular acidification rate (ECAR), which was measured by Cytosensor microphysiometry, was significantly reduced in the aortic VSMCs from the cirrhotic rats as compared to those from the control animals. The ability of AT-Ⅱ to promote formation of inositol phosphates, the second messenger produced by the activation of Gq-coupled receptors, was also considerably suppressed in the cirrhotic VSMCs. Furthermore, the maximal p42/44 MAPK phosphorylation stimulated by AT-Ⅱ was significantly reduced in the cirrhotic VSMCs in contrast to that in the normal VSMCs. Taken together, our data clearly demonstrated that the functional responses to AT-Ⅱ was severely suppressed in aortic VSMCs in cirrhosis, indicating the impairment of general Gq-coupled receptor signaling and subsequent biological function in the cirrhotic VSMCs.
文摘Angiotensin Ⅱ immunoreactivity (ir-Ang Ⅱ) was measured in brain areas,known to be involved in the control of circulation, in spontaneously hypertensive rats(SHR) and normotensive, Wistar Kyoto rats as controls (WKY) of 1-]2 weeks old and of both sexes. The systolic pressure (SP), in rats of 4-12 weeks old,increased with age and was signifficantly higher in SHR than WKY. In SHR, the increase was also significantly greater in male than female. The ir-Ang Ⅱ increased with age in all cardiovascular brain areas up to 12 weeks old in SHR, but only up to 4 weeks old in WKY. There was also sex difference in SHR. The changes in ir-Ang Ⅱ, particularly in the ventrolateral medulla (VLM), correlated well with changes in SP. The findings suggest thal interaction between brain Ang Ⅱ and cardiovascular brain areas, particularly the VLM and hypothalamus, may be crucial in the development of hypertension. The results also indicale sexual dimorphism in brain Ang Ⅱ in addition to blood pressure reaction in the developing SHR.
基金National "Ninth five-year" Key Technology R&D Programme of China (Grant No.99-929-01-31)
文摘To investigate the effects of icariin （ICA） on angiotensin Ⅱ（Ang Ⅱ）-induced injury in human umbilical vein endothelial cells line （ECV-304）. The ECV-304 cells were cultured in vitro. After 24 h incubating with icariin, the model of AngⅡ-induced injury in ECV-304 was established. The cell viability （MTT method）, Lactate dehydrogenase （LDH） release and Nitric oxide （NO） production in the medium, the capacity of scavenging superoxide anion radicals （O2^-） and hydroxyl radicals （.OH） were measured. The activities of superoxide dismutase （SOD）, total nitric oxide synthase （T-NOS）, inducible nitric oxide synthase （iNOS） and constitutive nitric oxide synthase （cNOS） in the cells were determined. Compared with the Ang Ⅱ-treated group, ICA can significantly raise the viability of EC, increase the activities of SOD, T-NOS and cNOS, increase the production of NO, enhance the capacity of scavenging superoxide anion radicals （ O2^- ） and hydroxyl radicals（.OH）, and lower LDH leakage and iNOS activity. The results suggest that ICA can protect endothelial cells （ECV-304） from Ang II-induced injury.
基金a grant from National Natural Sciences Foundation of China (No. 30500657)
文摘The changes of proto-oncogene c-fos and c-jun mRNA expression in angiotensin Ⅱ （AngⅡ）-induced hypertrophy and effects of sodium tanshinone ⅡA sulfonate （STS） in the primary culture of neonatal rat cardiomyocytes were investigated. Twelve neonatal clean grade Wistar rats were selected. The cardiomyocytes were isolated, cultured and divided according to different treatments in the medium. The cardiomyocyte size was determined by phase contrast microscope, and the rate of protein synthesis was measured by [3H]-Leucine incorporation. The c-fos and c-jun mRNA expression in cardiomyocytes was detected by reverse transcription polymerase chain reaction （RT-PCR）. It was found after cardiomyocytes were treated with AngⅡ for 30 min, the c-fos and c-jun mRNA expression in cardiomyocytes was increased significantly （P〈0.01）. After treatment with AngⅡ for 24 h, the rate of protein synthesis in AngⅡ group was significantly increased as compared with control group （P〈0.01）. After treatment with AngⅡ for 7 days, the size of cardiomyocytes in AngⅡ group was increased obviously as compared with control group （P〈0.05）. After pretreatment with STS or Valsartan before AngⅡ treatment, both of them could inhibit the above effects of AngⅡ （P〈0.05 or P〈0.01）. It was suggested that STS could ameliorate AngⅡ-induced cardiomyocyte hy- pertrophy by inhibiting c-fos and c-jun mRNA expression and reducing protein synthesis rate of cardiomyocytes.
