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To investigate the effects of leonurine(Leo) on abdominal aortic constriction(AAC)-induced cardiac hypertrophy in rats and its mechanism. A rat model of pressure overload-induced cardiac hypertrophy was established by AAC method. After 27-d intervention with high-dose(30 mg·kg~(-1)) and low-dose(15 mg·kg~(-1)) Leo or positive control drug losartan(5 mg·kg~(-1)), the cardiac function was evaluated by hemodynamic method, followed by the recording of left ventricular systolic pressure(LVSP), left ventricular end-diastolic pressure(LVESP), as well as the maximum rate of increase and decrease in left ventricular pressure(±dp/dt_(max)). The degree of left ventricular hypertrophy was assessed based on heart weight index(HWI) and left ventricular mass index(LVWI). Myocardial tissue changes and the myocardial cell diameter(MD) were measured after hematoxylin-eosin(HE) staining. The contents of angiotensin Ⅱ(AngⅡ) and angiotensin Ⅱ type 1 receptor(AT1 R) in myocardial tissue were detected by ELISA. The level of Ca~(2+) in myocardial tissue was determined by colorimetry. The protein expression levels of phospholipase C(PLC), inositol triphosphate(IP3), AngⅡ, and AT1 R were assayed by Western blot. Real-time quantitative PCR(qRT-PCR) was employed to determine the mRNA expression levels of β-myosin heavy chain(β-MHC), atrial natriuretic factor(ANF), AngⅡ, and AT1 R. Compared with the model group, Leo decreased the LVSP, LVEDP, HWI, LVWI and MD values, but increased ±dp/dt_(max) of the left ventricle. Meanwhile, it improved the pathological morphology of myocardial tissue, reduced cardiac hypertrophy, edema, and inflammatory cell infiltration, decreased the protein expression levels of PLC, IP3, AngⅡ, AT1 R, as well as the mRNA expression levels of β-MHC, ANF, AngⅡ, AT1 R, c-fos, and c-Myc in myocardial tissue. Leo inhibited AAC-induced cardiac hypertrophy possibly by influencing the RAS system.
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Animals , Rats , Angiotensin II/metabolism , Cardiomegaly/genetics , Gallic Acid/analogs & derivatives , Hypertrophy, Left Ventricular/pathology , Myocardium/pathologyABSTRACT
As of August 16,2021,there have been 207,173,086 confirmed cases and 4,361,996 deaths due to the coronavirus disease(COVID-19),and the pandemic remains a global challenge.To date,no effective and approved drugs are available for the treatment of COVID-19.Angiotensin-converting enzyme 2(ACE2)plays a crucial role in the invasion into host cells by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the etiological agent of COVID-19.Notably,ACE2 density is influenced by medical con-ditions,such as hypertension,or by drugs,including angiotensin-converting enzyme inhibitors(ACEIs)and angiotensin receptor blockers(ARBs),which can change the fate of SARS-CoV-2 infectivity.ACE2 is a target for these drugs and can be manipulated to limit the viral entry and replication within the cells.Different strategies aimed at blocking ACE2 with small molecules,peptides,and antibodies,or by neutralizing the virus through its competitive binding with human recombinant soluble ACE2(hrsACE2)are currently under investigation.In this article,we review the current state of knowledge that em-phasizes the need to find effective therapeutic agents against COVID-19 by exploiting ACE2 as a potential target.The increased soluble ACE2 levels and the application of hrsACE2 in patients with COVID-19 can be implemented to control the disease.It has not yet been established whether hypertension and other comorbidities,independent of age,have a direct role in COVID-19.Therefore,the use of renin-angiotensin system inhibitors,ACEls and ARBs,should not be discontinued during COVID-19 treatment.
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Objective:To study the effect of Fushengong prescreption on the regulation-antagonism effect of angiotensin converting enzyme-angiotensin Ⅱ-angiotensin Ⅱ 1 receptor （ACE-AngⅡ-AT1R） axis and angiotensin converting enzyme 2-angiotensin （1-7）-Mas receptor［ACE2-Ang（1-7）-MASR］ axis of rats with chronic renal failure（CRF）， and to explore its mechanism of delaying the development of CRF. Method:The 65 male SD rats were randomly divided into normal group （<italic>n</italic>=10） and modeling group （<italic>n</italic>=55）. The normal group was routinely reared， while the modeling group were administered by gavage with 0.25 g·kg<sup>-1</sup>d<sup>-1 </sup>adenine suspension for 28 days. After the model was successfully established， the survival model rats were randomly divided into model group， benazepril group（0.01 g·kg<sup>-1</sup>·d<sup>-1</sup>）and low，medium and high dose of Fushengong prescreption groups （4，8，16 g·kg<sup>-1</sup>·d<sup>-1</sup>）. The normal group and model group were administered the same volume of normal saline by gavage， lasted for 28 days. After the experiment， systolic blood pressure （SBP） and diastolic blood pressure （DBP） of caudal artery were measured， and 24-hour urine was collected to determine 24-hour urine protein （24 h U-pro）. The content of serum creatinine（SCr） and blood urea nitrogen （BUN） in the serum were measured， the histological morphology was observed by hematoxylin eosin（HE）staining， and the degree of renal interstitial fibrosis was observed by Masson staining. Enzyme linked immunosorbent assay （ELISA） was used to determine the contents of AngⅡ， Ang （1-7） and Cystatin C （CysC） in serum and renal homogenate. The protein level of ACE， ACE2， AT1R and MASR were detected by Western blot. The expression of ACE and ACE2 protein in renal tissues were detected by immunohistochemistry. Result:Compared with normal group， the expression levels of SCr， BUN and CysC in model group were significantly increased（<italic>P</italic><0.05）， the content of AngⅡ in serum and kidney tissues were significantly increased， the content of Ang （1-7） were significantly decreased（<italic>P</italic><0.05）， the expression of ACE and AT1R protein in renal tissues were significantly increased（<italic>P</italic><0.05）， and the expression of ACE2 and MASR protein were significantly decreased（<italic>P</italic><0.05）. Compared with model group and benazepril group， after the intervention with Fushengong prescreption， the serum SCr，BUN and CysC decreased（<italic>P</italic><0.05），the content of AngⅡ in serum and kidney tissues decreased significantly，Ang（1-7） increased significantly（<italic>P</italic><0.05）， the expression of ACE and AT1R protein in renal tissues decreased significantly（<italic>P</italic><0.05）， ACE2 and MASR protein increased significantly（<italic>P</italic><0.05）. The high-dose Fushengong prescreption has the best effect. The high， medium and low-dose effects of Fushengong prescreption were dose-dependent. Conclusion:Fushengong prescreption improved renal function and pathological change of kidney in adenine-induced rats with chronic renal failure. The mechanism may be related to the inhibition of ACE-AngⅡ-AT1R axis and promotion of ACE2-Ang（1-7）-MASR axis ，which leads to the delaying of the progression of chronic renal failure.
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Objective:To investigate the effects of notoginsenoside R1 （NR1） on the proliferation of mice aortic smooth muscle cells （MOVAS cells） induced by angiotensinⅡ （AngⅡ） and the signal pathway of angiotensin Ⅱ type 1 receptor （AT1R） / mitogen activated protein kinases （MAPKs）. Methods:The proliferation of MOVAS cells was detected by BrdU method after AngⅡ induction. Western blot was used to detect the expression of the two main receptors of AngⅡ （AT1R and AT2R） and MAPKs pathway related proteins （ERK， p38， and JNK）. Results:（1） AngⅡ （5 μmol/L） could promote the proliferation of MOVAS cells （P<0.01）. NR1 （50 μmol/L） could inhibit the proliferation of MOVAS cells induced by AngⅡ （P<0.01）. There was no significant difference between control group and NR1 group （P>0.05）. （2） Compared with AngⅡ group， the expression of AT1R protein in AngⅡ+ NR1 group was significantly lower （P<0.05）， but there was no difference in the expression of AT2R protein （P>0.05）. （3） NR1 could significantly inhibit the phosphorylation of ERK， p38 and JNK protein after AngⅡ stimulation （P<0.01）. Conclusion:NR1 can inhibit the proliferation of MOVAS cells induced by AngⅡ， which may be related to down regulating AT1R and inhibiting the activation of MAPKs.
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Objective: To study the therapeutic effect of Kangxianling decoction on renal fibrosis induced by 5/6 nephrectomy, and angiotensin converting enzyme-angiotensin Ⅱ-angiotensin Ⅱ 1 receptor (ACE-AngⅡ-AT1R) axis. Method: Totally 50 SD rats were randomly divided into the following groups:control group (n=10), sham-operation group (n=10), 5/6 nephrectomized renal fibrosis model group (n=30). After two weeks, the rats in operation group were divided into the model group, Kangxianling group, and losartan potassium group, n=10 in each group. Rats in losartan potassium group were administered with losartan potassium by gastrogavage, and rats in Kangxianling group were administered with Kangxianling by gastrogavage. Equal volume of saline was administered to rats in the other groups. The rats were put to death after 16 weeks of consecutive medication, and serum creatinine(SCr), blood urea nitrogen(BUN), 24 h urine protein(24 h-Pro) were measured in each group. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of kidney tissues, and the degree of renal fibrosis was observed by Masson staining. The expressions of ACE1 and AT1R were detected by immunohistochemistry. The protein expression levels of ACE1, AngⅡ and AT1R were determined by Western blot. Result: Compared with control and sham-operation groups, SCr, BUN and 24 h-Pro in model group were significantly increased (PPPPConclusion: Kangxianling decoction can delay the progress of renal fibrosis in 5/6 nephrectomized rats, which is closely related to the inhibition of ACE-AngⅡ-AT1R axis activation.
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Objective:To identify the proliferation effect and angiogenic ability of CXCL4 on human dermal microvascular endothelial cells(HDMECs),and to explore the secretion of vasomotion factors.Methods:HDMECs were treated with gradient concentration to test the proliferation of HDMECs.CCK-8 was used to explicated the proliferation of HDMECs.The effect of CXCL4 on angiogenic ability of HDMECs was determined by tube formation assay.The mRNA levels of endothelin-1(ET-1),Fli-1,AngiotensinⅡtype 1 receptor(AT1R) and endothelin-1 type A receptor (ETAR) were detected by real-time quantitative polymerase chain reaction (Real-time PCR).Results:The specific receptor of CXCL4 was expressed on HDMECs.CXCL4 could inhibit the proliferation of HDMECs and the number of tube formation in a dose-depend manner.After CXCL4 intervention,the relative amplification multiples of ET-1,AT1R were significantly increased(P<0.05),Fli-1 was decreased(P<0.05),and ETAR had no change as compared with the control group.Furthermore,CXCL4 antagonist could reverse the effects of CXCL4 on HDMECs.Conclusion:CXCL4 inhibit the proliferation and angiogenesis of HDMECs and induce the secretion of ET-1 and AT1R,reduce the secretion of Fli-1 in a dose-dependent manner.
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It has been previously demonstrated that the hemodynamic effect induced by angiotensin II (AII) in the liver was completely abolished by losartan while glucose release was partially affected by losartan. Angiotensin II type 1 (AT1) and adrenergic (∝1- and β-) receptors (AR) belong to the G-proteins superfamily, which signaling promote glycogen breakdown and glucose release. Interactive relationship between AR and AT1-R was shown after blockade of these receptors with specific antagonists. The isolated perfused rat liver was used to study hemodynamic and metabolic responses induced by AII and adrenaline (Adr) in the presence of AT1 (losartan) and ∝1-AR and β-AR antagonists (prazosin and propranolol). All antagonists diminished the hemodynamic response induced by Adr. Losartan abolished hemodynamic response induced by AII, and AR antagonists had no effect when used alone. When combined, the antagonists caused a decrease in the hemodynamic response. The metabolic response induced by Adr was mainly mediated by ∝1-AR. A significant decrease in the hemodynamic response induced by Adr caused by losartan confirmed the participation of AT1-R. The metabolic response induced by AII was impaired by propranolol, indicating the participation of β-AR. When both ARs were blocked, the hemodynamic and metabolic responses were impaired in a cumulative effect. These results suggested that both ARs might be responsible for AII effects. This possible cross-talk between β-AR and AT1-R signaling in the hepatocytes has yet to be investigated and should be considered in the design of specific drugs.
Subject(s)
Animals , Male , Receptors, Adrenergic, alpha/physiology , Receptors, Adrenergic, beta/physiology , Receptor, Angiotensin, Type 1/physiology , Glucose/metabolism , Hypertension, Portal/metabolism , Liver/metabolism , Propranolol/pharmacology , Time Factors , Prazosin/pharmacology , Receptors, Adrenergic, alpha/drug effects , Receptors, Adrenergic, beta/drug effects , Rats, Wistar , Adrenergic beta-Antagonists/pharmacology , Losartan/pharmacology , Receptor, Angiotensin, Type 1/drug effects , Angiotensin II Type 1 Receptor Blockers/pharmacology , Angiotensin Receptor Antagonists/pharmacology , Hemodynamics/drug effects , Hemodynamics/physiology , Liver/drug effectsABSTRACT
<p><b>OBJECTIVE</b>To observe the effects of electroacupuncture (EA) on postoperative cognitive dysfunction (POCD) and AngⅡ/AT1R in the hippocampus in D-galactose-induced aging rats which received hepalobectomy, and to explore the possible mechanism of EA on POCD.</p><p><b>METHODS</b>Eighty male Sprague-Dawley rats were randomly divided into a young control group (10 rats), a D-Galactose-induced aged (Da) group (10 rats), a Da+hepatolobectomy group (30 rats) and an EA group (30 rats). The rats in the Da+hepatolobectomy group and EA group were further randomly divided into a 1 d subgroup, 3 d subgroup and a 7 d subgroup, 10 rats in each subgroup. The rats in the EA group were treated with EA at "Baihui" (GV 20) and "Dazhui" (GV 14) with continuous wave (15 Hz in frequency and 1 mA in intensity), and rats in each subgroup were treated for 1 d, 3 d and 7 d, respectively. The rats in the remaining groups were treated with immobilization, once a day. The Y-maze was used to observe the behavior change of rats, and ELISA was applied to measure the level of hippocampal AngⅡ, and RT-PCR and immunohistochemistry method were performed to detect AT1R mRNA expressions and AT1R positive expression in the hippocampus.</p><p><b>RESULTS</b>The number of rat initiative avoidance in the Da group was significantly less than that in the young control group (<0.05), and the mRNA expression and positive percentage of AT1R in the hippocampus in the Da group were significantly higher than those in the young control group (both<0.01). Compared with the Da group, the number of rat initiative avoidance in each subgroup of Da+hepatolobectomy group and EA group were significantly reduced (all<0.01), and the expression of AngⅡ, AT1R mRNA and AT1R positive cells percentage in the hippocampus were significantly increased (<0.05,<0.01). The number of rat initiative avoidance in each subgroup of EA group was higher than that in the subgroup of Da+hepatolobectomy group (<0.05,<0.01); and the expression of AngⅡ, AT1R mRNA, and AT1R positive percentage in the EA group were significantly less than that in the Da+hepatolobectomy group (<0.05,<0.01).</p><p><b>CONCLUSIONS</b>EA at "Baihui" (GV 20) and "Dazhui" (GV 14) could improve POCD in D-galactose-induced aging rats which received hepalobectomy, and it is likely to be related with the inhibition of AngⅡ, AT1R positive expression and AT1R mRNA in the hippocampus.</p>
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Initially,the renin-angiotensin system (RAS) was considered to play an important role in regulating cardiovascular function and maintaining the balance of water and electrolyte.Based on this,several targeted drugs in the treatment of hypertension were developed.With the large-scale clinical apphcation of these drugs,RAS inhibitors are found to has a significant inhibitory effect on some of the tumor development,which reveals the RAS function in cell proliferation,differentiation,angiogenesis and tumor occurrence.In this paper,the important physiological ftmction of RAS in tumor occurrence and development were reviewed.
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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, l 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 Longa 5-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 AT1R 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 immunohistochemical assay indicated that microRNA-155 inhibitor could up-regulate the expression of CD31, while microRNA-155 mimic could down-regulate the expression of CD31. The RT-PCR found that, after being treated with microRNA-155 inhibitor, MACO rats had the increased expression of AT1R and VEGFR2 messenger RNA (mRNA); but after being treated with microRNA-155 mimic, the expression of AT1R and VEGFR2 mRNA was decreased. Results of Western blot showed that, after being treated with microRNA-155 inhibitor, MACO rats had the increased expression of AT1R and VEGFR2 mRNA; but after being treated with microRNA-155 mimic, the expression of AT1R and VEGFR2 mRNA was decreased.@*CONCLUSIONS@#The inhibition of microRNA-155 can improve the neurologic impairment of rats with the cerebral infarction, reduce the volume of cerebral infarction and effectively promote the angiogenesis in the region of ischemia, which may be mediated through AT1R/VEGFR2 pathway.
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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, l 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 Longa 5-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 AT1R 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 immunohistochemical assay indicated that microRNA-155 inhibitor could up-regulate the expression of CD31, while microRNA-155 mimic could down-regulate the expression of CD31. The RT-PCR found that, after being treated with microRNA-155 inhibitor, MACO rats had the increased expression of AT1R and VEGFR2 messenger RNA (mRNA); but after being treated with microRNA-155 mimic, the expression of AT1R and VEGFR2 mRNA was decreased. Results of Western blot showed that, after being treated with microRNA-155 inhibitor, MACO rats had the increased expression of AT1R and VEGFR2 mRNA; but after being treated with microRNA-155 mimic, the expression of AT1R and VEGFR2 mRNA was decreased. Conclusions: The inhibition of microRNA-155 can improve the neurologic impairment of rats with the cerebral infarction, reduce the volume of cerebral infarction and effectively promote the angiogenesis in the region of ischemia, which may be mediated through AT1R/VEGFR2 pathway.
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Background and purpose:Studies have shown that renin-angiotensin system (RAS) is closely associated with tumor progress. angiotensinⅡ (AngⅡ) is the most important component of RAS. This study aimed to investigate the possible mechanism by which AngⅡ affected the cell proliferation in human breast cancer cell line MCF-7.Methods:CCK-8 was used to investigate the cell proliferation alteration of MCF-7 cells after treatment of AngⅡ at different dose and time. The inlfuence of losartan (an AT1R inhibitor) and PD98059 (a MAPK inhibitor) in AngⅡ-enhanced cell proliferation was detected by CCK-8. Protein expression was analyzed by Western blot.Results:AngⅡ stimulated the growth of breast cancer cells in a dose- and time-dependent manner. The maximal proliferation effect on MCF-7 cells was obtained with 10-7 mol/L AngⅡ and 24 h, respectively (P<0.000 1). Losartan signiifcantly decreased the level of AngⅡ-induced proliferative effects (P<0.05). Western blot showed that AngⅡ caused rapid activation of p-ERK. In addition, PD98059 could signiifcantly suppress AngⅡ-promoted cell proliferation.Conclusion:AngⅡ can promote MCF-7 cell proliferation through AT1R/ERK/MAPK pathway activation, which could be reversed by losartan or PD98059. Therefore, targeting AngⅡ/AT1R/MAPK signaling could be a novel therapeutic for breast cancer.
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Objective Through establishing a rat model of atrial fibrillation,to study myocardial angiotensin type Ⅰ (AT1R) and type Ⅱ receptor (AT2R) mRNA expression levels in of the state atrial fibrillation and Artemisia annua extract on its expression.Methods Rat model of atrial fibrillation was established,Artemisia annua extract was used for intervention and captopril was adopted as controls.AT1R,AT2R mRNA and protein expression were observed by PCR and Western-blot technology.Results Compared with the control group (0.36±0.05),myocardial AT1R mRNA expression was significantly increased in the model group (0.84±0.04) (P＜0.05).BothArtemisia annua (0.56±0.03) and captopril (0.53±0.04) could significantly reduce the myocardial AT1R mRNA expression in the atrial fibrillation rats (P＜0.05).Captopril showed obvious AT1R mRNA reduction trend,but there was statistical significance compared with Artemisinic extract (P＞0.05).Artemisinic extract showed no impact on AT2R mRNA expression.Conclusion AT1R was closely related to the incidence of atrial fibrillation.AT1R expression was significantly increased in atrial fibrillation rat.The artemisinic extract can be effectively reduced fibrillation myocardial AT1R expression,which may link with its artemisinic antiarrhythmic mechanism.
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SN Ⅱ A on TGF betal/Smads signal pathway in local myocardium.
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Objective:To study the effect of compound Biejiaruangan tablets on the expression of liver AngiotensionII and its receptor in rats with hepatic fibrosis,and to explore the mechanism of its anti-hepatic fibrosis.Methods: Thirty male SD rats were randomly divided into three groups as followings: the normal group,the model group and the compound Biejiaruangan tablets group,all rats in the two latter groups were given subcutaneous injection of 40%carbon tetrachloride(twice every week for 6 weeks),the rats in the compound Biejiaruangan tablets group were given 1g?kg-1?d-1 of the compound Biejiaruangan tablets by daily gavage,the rats in normal control group and the model group were given distilled water according to the same volume,the histopathological changes in liver were observed through HE and Massion staining.The serum ALT,AST and ALP were evaluated by antomatic biochemistry analysator,the serum levels of hyaluronic acid (HA),Laminin(LN) and plasm AngiotensionII(Ang-Ⅱ) were determined by radio immunoassay.The expressions of AngⅡ,AT1R mRNA were examined by RT-PCR.Results:The severity of inflammation scoring,hepatic fibrosis scoring,the amounts of serum ALT,AST,ALP,HA,LN and plasma AngⅡ in the liver tissues of hepatic fibrosis model group were higher than those in the normal group(P
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Objective To explore the mechanisms of angiotensin Ⅱ (Ang Ⅱ) induced apoptosis of cultured cardiomyocytes of neonatal rats. Methods Cultured neonatal rat cardiomyocytes were divided into three groups. Cells in the control group were incubated in serum-free medium for 2, 6, 12, and 24 h. Cells in Ang Ⅱ group were incubated with Ang Ⅱ at the dose of 10 -7 mol/L for 2, 6, 12, and 24 h. Cells in Ang Ⅱ and Ang Ⅱ type 1 receptor antagonist group were incubated in medium containing 10 -7 mol/ L Ang Ⅱ plus 10 -5 mol/L irbesartan. The apoptotic cells were detected by TUNEL assay. The Bcl-2 protein expression was assessed by immunohistochemistry. Caspase-3 activity was measured by a fluorescent assay kit. Results The number of apoptotic cells in Ang Ⅱ group increased significantly in a time-dependent manner, accompanied by decreased Bcl-2 protein expression but increased activity of caspase-3. Treatment with irbesartan resulted in decreased number of apoptotic cells and decreased activity of caspase-3. Conclusion Angiotensin Ⅱ could induce the apoptosis of neonatal rat cardiomyocytes through the caspase-dependent pathway, which might be mediated by Ang Ⅱ type 1 receptor. Bcl-2 may participate in the regulation.
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Objective To explore the relationship between angiotensin I-converting enzyme(ACE)gene I/D and angiotensin Ⅱ type 1 receptor(AT1R)gene A1166C polymorphisms and cereral infarction(CI).Methods ACE and AT1R genotypes were investigated with the method of PCR-RLFP in 88 patients with CI and compared with 90 age-matched population controls.Results AC genotypic frequency(31.8%)and C allele frequency(15.9%)of AT1R gene in CI group were significently higher than those in control group(11.1%,5.6%)(all P0.05).Conclusions The polymorphism of AT1R A1166C is related to the incidence of CI.There are synergistic effects of ACE DD genotype and AT1R gene A1166C polymorphisms on the risk of CI.