心力衰竭时大鼠下丘脑室旁核内血管紧张素1型受体的变化对交感神经活动的影响

目的观察心力衰竭时大鼠下丘脑室旁核内血管紧张素1型受体(AT1-R)可能发生的改变及其对交感神经活动的影响。方法选取雄性SD大鼠,首先进行室旁核插管术,1周后采用左侧冠状动脉结扎术建立大鼠心力衰竭模型或假手术模型,同时各组大鼠分别经微型渗透泵通过室旁核插管持续给予AT1-R阻滞剂缬沙坦(VAL)0.05μg/h或人工脑脊液(aCSF)0.11μl/h干预。4周后检测心功能;电生理记录肾交感神经放电;计算肺/体质量比(L/BW)和右心室/体质量比(RVW/BW);测定血浆去甲肾上腺素(NE)和血管紧张素Ⅱ(AngⅡ)含量;Western blot技术检测下丘脑室旁核内Fra-like和AT1-R蛋白表达情况。结果与假手术组比较,冠状动脉结扎术后4周大鼠的心功能明显降低;血浆NE和AngⅡ浓度增高(P<0.05);肾交感神经放电明显增强;室旁核内Fra-like和AT1-R蛋白表达增加(P<0.05)。与人工脑脊液治疗组比较,接受缬沙坦治疗的心力衰竭大鼠心功能有所改善,外周血NE和AngⅡ含量下降(P<0.05),肾交感神经放电减少(P<0.05),室旁核区域的Fra-like和AT1-R表达明显减少(P<0.05)。结论心力衰竭时室旁核区域的AT1-R被明显激活伴有交感神经放电增加,促进心力衰竭的发展。     

下丘脑室旁核内血管紧张素转换酶对心力衰竭大鼠交感神经活动的影响

目的观察心力衰竭时大鼠下丘脑室旁核内血管紧张素转换酶(ACE)的变化及其对心力衰竭发生发展和交感神经活动的影响。方法选取雄性SD大鼠36只,室旁核插管术后1周采用冠状动脉结扎术建立大鼠心力衰竭模型或假手术模型,同时室旁核插管连接微型渗透泵分别持续给予血管紧张素转换酶抑制剂赖诺普利(Lisinopril,0.46g/h.PVN)或空白对照药(Vehicle,0.11l/h.PVN)干预。4周后血流动力学检测心功能;记录肾交感神经放电活动;计算肺/体质量比(Lung/BW)和右心室/体质量比(RVW/BW);酶联免疫吸附试验(ELISA)法测定血浆NE和AngII含量;免疫组织化学染色观察室旁核ACE表达的变化;Western blot测定室旁核Fra-like蛋白含量。结果与假手术组比较心力衰竭大鼠左心室舒张末压(LVEDP)明显升高,左心室内压力最大上升或下降速率(±dp/dt max)和射血分数(LVEF)明显下降,左室前负荷增加(RVW/BW和Lung/BW明显升高,P<0.05);肾交感神经放电明显增强;血浆NE和AngII浓度增高(P<0.05);室旁核内Fra-like和ACE表达增加(P<0.05)。与Vehicle治疗的心力衰竭大鼠比较,接受赖诺普利治疗后心力衰竭大鼠LVEDP、RVW/BW和lung/BW有所降低(P<0.05),±dp/dtmax升高(P<0.05),LVEF无明显改变,外周血NE和ANGII含量下降(P<0.05),室旁核Fra-like和ACE表达明显减少(P<0.05),肾交感神经放电减少(P<0.05)。结论心力衰竭时室旁核ACE被明显激活引起交感神经放电增加,心功能减退。     

脑内肿瘤坏死因子-α参与高血压发病机制的研究

目的探讨脑内肿瘤坏死因子(TNF)-α通过调节下丘脑室旁核去甲肾上腺素影响高血压大鼠交感神经活动的机制。方法雄性成年SD大鼠,将血管紧张素Ⅱ(ANGⅡ)溶解在生理盐水中由静脉内以10ng.kg-1.min-1持续给药4周制作高血压模型,对照组大鼠给予生理盐水,治疗组通过侧脑室给予TNF-α阻断剂己酮可可碱(PTX)4周,非治疗组给予人工脑脊液(aCSF)4周。大鼠分为高血压治疗组(ANGⅡ+PTX)、高血压非治疗组(ANGⅡ+aCSF)、对照治疗组(生理盐水+PTX)和对照非治疗组(生理盐水+aCSF)。4周后采用高效液相色谱法(HPLC)测量下丘脑室旁核和血浆中去甲肾上腺素水平。结果高血压大鼠下丘脑室旁核和血浆中去甲肾上腺素水平升高(P<0.05),经侧脑室给予PTX4周后可降低下丘脑室旁核和血浆中去甲肾上腺素水平(P<0.05)。结论脑内TNF-α可通过调节下丘脑室旁核去甲肾上腺素水平参与高血压的发病机制,阻断中枢TNF-α合成可在一定程度上降低交感神经兴奋性。     

芪苈强心胶囊对慢性心衰大鼠下丘脑室旁核RAS系统及交感神经系统的影响

目的观察经侧脑室长期泵入芪苈强心胶囊对慢性心衰大鼠心功能、下丘脑室旁核内肾素-血管紧张素系统(RAS)血管紧张素Ⅱ(AngⅡ)、血管紧张素转换酶(ACE)、血管紧张素Ⅰ型受体(AT_1R)及外周交感神经活性的影响。方法采用结扎冠状动脉左前降支建立急性心肌梗死致心衰模型,造模4周后,经侧脑室插管连接微量注射泵,分别给予醇化芪苈强心溶液和阳性药氯沙坦,给药4周后,应用超声心动图测定各组大鼠心功能变化,HE染色观察心肌组织形态,酶联免疫法测定血浆去甲肾上腺素(NE)、血清N端前脑钠肽(NT-proBNP)及室旁核内AngⅡ含量变化,Real-time PCR和Western blot方法测定室旁核ACE、AT_1R mRNA及蛋白表达水平,PowerLab多通道生理记录仪测定各组肾交感神经活性的变化。结果与假手术组比较,模型组大鼠心功能明显降低,下丘脑室旁核内AngⅡ、ACE、AT_1R表达水平及NE、NT-proBNP表达水平明显升高,肾交感神经放电活性增强;与模型组比较,各给药组均可不同程度改善心衰大鼠心功能,减轻心肌组织形态改变,降低下丘脑室旁核AngⅡ、ACE、AT_1R及NE、NT-proBNP表达水平,降低肾交感神经放电活性。结论经侧脑室连接微量注射泵给予芪苈强心胶囊可降低下丘脑室旁核内RAS系统的激活,降低肾交感神经的活性,改善慢性心衰大鼠心功能,延缓心衰的进展。     

黄连素对EAE大鼠小胶质细胞及细胞因子的影响

目的探讨黄连素(berberine,Ber)对实验性自身免疫性脑脊髓炎(encephalomyelitis,EAE)大鼠脊髓中小胶质细胞及IFN-γ、TNF-α和IL-10水平的影响。方法 Lewis大鼠24只随机分为3组:对照组、模型组和Ber组。采用免疫组化法检测腰髓中小胶质细胞的变化;采用ELISA法检测大鼠外周血和颈髓中促炎因子IFN-γ、TNF-α和抑炎因子IL-10的变化。结果模型组8只大鼠全部出现典型的EAE行为学改变,Ber组有3只大鼠出现EAE行为学改变。与模型组相比,Ber组大鼠外周血中IFN-γ和TNF-α表达降低(P<0.05),而IL-10的表达无明显变化;脊髓中活化的小胶质细胞数量减少,IFN-γ和TNF-α表达降低(P<0.05),IL-10表达增加(P<0.05)。结论 Ber能抑制大鼠EAE的病情,其机制可能与抑制小胶质细胞的活化,下调IFN-γ、TNF-α的表达,并且上调IL-10的表达有关。     

氯沙坦通过室旁核抑制慢性心衰大鼠肾交感神经兴奋性

目的：研究慢性心衰时室旁核微量注射氯沙坦对心率、血压和肾交感神经的作用,揭示心衰下丘脑室旁核对肾交感神经活性的调节机制。方法：用SD大鼠制作心衰模型,超声心动图检测心功能变化。脑立体定位仪对大鼠室旁核定位,微量注射氯沙坦（50nL）,观察心率、血压和肾交感神经活性的变化。结果：超声心动图显示手术组较假手术组左室内径增加（P〈0．01）,射血分数降低（P〈0．01）,左室内径缩短率降低（P〈0．05）。注射氯沙坦后,手术组和假手术组的肾交感神经兴奋性降低,手术组较假手术组降低更为明显。结论：心衰时室旁核内注射氯沙坦可降低肾交感神经兴奋性。     

氯沙坦通过室旁核抑制慢性心衰大鼠肾交感神经兴奋性

目的：研究慢性心衰时室旁核微量注射氯沙坦对心率、血压和肾交感神经的作用,揭示心衰下丘脑室旁核对肾交感神经活性的调节机制。方法：用SD大鼠制作心衰模型,超声心动图检测心功能变化。脑立体定位仪对大鼠室旁核定位,微量注射氯沙坦（50nL）,观察心率、血压和肾交感神经活性的变化。结果：超声心动图显示手术组较假手术组左室内径增加（P〈0．01）,射血分数降低（P〈0．01）,左室内径缩短率降低（P〈0．05）。注射氯沙坦后,手术组和假手术组的肾交感神经兴奋性降低,手术组较假手术组降低更为明显。结论：心衰时室旁核内注射氯沙坦可降低肾交感神经兴奋性。     

淫羊藿苷对去卵巢大鼠骨和下丘脑不同核团ERβ mRNA表达的影响

目的观察淫羊藿苷对去卵巢大鼠骨和下丘脑不同核团ERβmRNA表达的影响,探讨其治疗绝经后骨质疏松的作用机制。方法将10～11月龄SD♀大鼠60只,随机分为假手术组、去卵巢模型组、淫羊藿苷小、中、大剂量组(每组12只)。以双侧卵巢切除法建立大鼠骨质疏松模型。分别用淫羊藿苷小、中、大剂量给药4个月,采用RT-PCR法,观察各组大鼠骨和下丘脑室旁核、视上核、弓状核ERβmRNA表达的变化。结果大鼠卵巢切除后,血清E2水平、椎骨骨密度、子宫湿重、胫骨和下丘脑弓状核ERβmRNA表达明显降低(P<0.01),下丘脑室旁核、视上核ERβmRNA表达均明显升高(P<0.01)。与去卵巢模型组比较,淫羊藿苷50.0和100.0 mg.kg-1组治疗后,血清E2水平、椎骨骨密度、胫骨和下丘脑弓状核ERβmRNA表达明显升高(P<0.01),下丘脑室旁核、视上核ERβmRNA表达均明显降低(P<0.01),子宫湿重无明显改变(P>0.05)。结论淫羊藿苷可以改善切除卵巢所致的骨质疏松大鼠的骨密度,对子宫无不良反应。其机制可能与其选择性调节去卵巢骨质疏松大鼠下丘脑不同核团ERβmRNA表达水平有关,调节下丘脑功能活动是其途径之一。     

安宫牛黄丸及朱砂和雄黄对脂多糖诱导的神经损伤的作用(英文)

目的探讨朱砂和雄黄在安宫牛黄丸(AGNH)配方中对脂多糖(LPS)介导的神经损伤的保护作用及机制。方法制备大鼠中脑原代神经元-神经胶质细胞联合培养模型。实验分为正常对照组、LPS 10μg.L-1模型组、LPS +朱砂(4和40 mg.L-1)组、LPS +雄黄(4和40 mg.L-1)组和LPS +AGNH(40和400mg.L-1)组。药物与细胞作用30 min后加入LPS;7 d后进行实验指标检测。采用免疫组织化学染色法检测酪氨酸羟化酶阳性的细胞数量和形态学变化以及小神经胶质细胞的激活情况,实时RT-PCR检测细胞中肿瘤坏死因子α(TNF-α)mRNA和诱导型一氧化氮合酶(iNOS)mRNA表达水平,酶联免疫吸附试验(ELISA)与Griess试剂分别检测细胞培养上清液中TNF-α和一氧化氮(NO)的含量。结果与正常对照组比较,LPS10μg.L-1作用于细胞,多巴胺能神经元的数量明显下降了40%(P<0.05);LPS显著诱导小神经胶质细胞的激活,TNF-αmRNA和iNOS mRNA的表达分别增加了9倍和2倍(P<0.05),同时神经元-胶质细胞联合培养上清液中TNF-α和NO的含量分别增加了20倍和30倍(P<0.05)。与LPS模型组比较,AGNH400mg.L-1和雄黄40 mg.L-1能明显拮抗LPS对多巴胺能神经元的毒性作用,多巴胺神经元数量分别上升了40%和30%(P<0.05);AGNH400 mg.L-1和雄黄40 mg.L-1能抑制小神经胶质细胞的激活,小胶质神经细胞中TNF-αmRNA分别下降了61%和52%(P<0.05)和iNOS mRNA的表达分别降低了58%和51%(P<0.05),而且神经元-神经胶质细胞联合培养上清液中TNF-α的含量分别降低了55%和43%(P<0.05)以及NO的含量分别下降了53%和34%(P<0.05)。而朱砂对LPS的作用无影响。结论 AGNH能改善LPS介导的神经元损伤,雄黄是其抗炎作用的有效成分之一,朱砂未见明显的神经保护作用。     

脊髓胶质细胞及前炎性细胞因子在慢性前列腺炎/慢性盆腔疼痛综合征大鼠中的作用及机制

目的探讨脊髓星形胶质细胞和小胶质细胞以及前炎性细胞因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子α(TNFα)在CP/CPPS发生发展中的作用及机制。方法 40只健康雄性Sprague-Dawley(SD)大鼠,随机分为正常不加任何处理的对照组(n=20)、CP/CPPS模型组(n=20),完全福氏佐剂和3%角叉菜胶前列腺内注射造成CP/CPPS模型。通过检测机械性痛阈(PWT)来评价动物痛行为学改变;采用免疫组织化学、逆转录多聚酶链反应(RT-PCR)等方法,检测脊髓星形胶质细胞GFAP和小胶质细胞OX-42的表达以及脊髓前炎性细胞因子IL-1β、IL-6及TNFαmRNA表达的变化,评价脊髓小胶质细胞和星形胶质细胞活化情况及脊髓前炎性细胞因子表达与疼痛行为改变的关系。结果与对照组比较,CP/CPPS模型组大鼠建模后第11天出现PWT明显降低(P<0.05),并呈进行性下降趋势;随着时间进程,免疫组化结果显示模型组动物脊髓小胶质细胞和星形胶质细胞依次活化,小胶质细胞活化开始于建模后第7天,星形胶质细胞活化开始于建模后第14天;模型组动物脊髓IL-1β、IL-6和TNFαmRNA表达较对照组明显增加(P<0.05)。结论在CP/CPPS大鼠中脊髓胶质细胞活化及前炎性细胞因子IL-1β、IL-6和TNFα的表达增加,可能在神经病理性疼痛的产生和维持中起着重要的作用。     

The role of oxidative stress in renovascular hypertension

1. There is mounting evidence that increased oxidative stress and sympathetic nerve activity play important roles in renovascular hypertension. In the present review, we focus on the importance of oxidative stress in two distinct populations of neurons involved with cardiovascular regulation: those of the rostral ventrolateral medulla (RVLM) and those of the paraventricular nucleus of the hypothalamus (PVN) in the maintenance of sympathoexcitation and hypertension in two kidney–one clip (2K1C) hypertensive rats. Furthermore, the role of oxidative stress in the clipped kidney is also discussed. 2. In the studies reviewed in this article, it was found that hypertension and renal sympathoexcitation in 2K1C rats were associated with an increase in Angiotensin II type one receptor (AT₁) expression and in oxidative markers within the RVLM, PVN and in the clipped kidneys of 2K1C rats. Furthermore, acute or chronic anti‐oxidant treatment decreased blood pressure and sympathetic activity, and improved the baroreflex control of heart rate and renal sympathetic nerve activity in 2K1C rats. Tempol or vitamin C administration in the RVLM, PVN or systemically all reduced blood pressure and renal sympathetic activity. Cardiovascular improvement in response to chronic anti‐oxidant treatment was associated with a downregulation of AT₁ receptors, as well as oxidative markers in the central nuclei and clipped kidney. 3. The data discussed in the present review support the idea that an increase in oxidative stress within the RVLM, PVN and in the ischaemic kidney plays a major role in the maintenance of sympathoexcitation and hypertension in 2K1C rats.     

Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin–angiotensin system and proinflammatory cytokines in hypertension

Aims

To explore whether reactive oxygen species (ROS) scavenger (tempol) in the hypothalamic paraventricular nucleus (PVN) attenuates renin–angiotensin system (RAS) and proinflammatory cytokines (PICs), and decreases the blood pressure and sympathetic activity in angiotensin II (ANG II)-induced hypertension.

Methods and results

Male Sprague–Dawley rats were infused intravenously with ANG II (10 ng/kg per min) or normal saline (NS) for 4 weeks. These rats were treated with bilateral PVN infusion of oxygen free radical scavenger tempol (TEMP, 20 μg/h) or vehicle (artificial cerebrospinal fluid, aCSF) for 4 weeks. ANG II infusion resulted in increased mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). These ANG II-infused rats also had higher levels of gp91^phox (a subunit of NAD(P)H oxidase), angiotensin-converting enzyme (ACE), and interleukin-1beta (IL-1β) in the PVN than the control animals. Treatment with PVN infusion of TEMP attenuated the overexpression of gp91^phox, ACE and IL-1β within the PVN, and decreased sympathetic activity and MAP in ANG II-infused rats.

Conclusion

These findings suggest that ANG II infusion induces elevated PICs and oxidative stress in the PVN, which contribute to the sympathoexcitation in hypertension. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin–angiotensin system, proinflammatory cytokines and oxidative stress in ANG II-induced hypertension.     

Furosemide Elicits Immediate Sympathoexcitation via a Renal Mechanism Independent of Angiotensin II

Abstract: This investigation aimed at examing the hypothesis that furosemide elicits renal sympathoexcitation through stimulation of renal renin release, which in turn produces increased plasma angiotensin II levels, causing centrally mediated sympathoexcitation. In addition, direct central nervous actions of furosemide on central control of mean arterial pressure, heart rate, and efferent renal sympathetic nerve activity were examined. Furosemide (300 mg/kg intravenously) was administered to four groups of rats: (1) control; (2) nephrectomized; (3) with intravenous losartan blockade (10 μmol/kg); and (4) with intracerebroventricular losartan blockade (10 nmol). In a fifth group of rats, furosemide was administered intracerebroventricularly (0, 2.5, 25 or 250 μg). To eliminate reflex control of mean arterial pressure, heart rate and efferent renal sympathetic nerve activity, all experiments were performed in rats with sinoaortic denervation and bilateral vagotomy. Experiments were performed during Saffan anaesthesia (0.9% alphaxalone/0.3% alphadolone), and rats were paralyzed with pancuronium and artifically ventilated. Furosemide produced an immediate 40% increase in efferent renal sympathetic nerve activity while the furosemide vehicle, 2 vol.% ethanolamine, did not affect efferent renal sympathetic nerve activity. The furosemide-induced increase in efferent renal sympathetic nerve activity was abolished in rats with bilateral nephrectomy but it was not affected by intravenous or intracerebroventricular losartan blockade. Intracerebroventricular angiotensin II produced an increase in mean arterial pressure and efferent renal sympathetic nerve activity whereas intravenous angiotensin II produced a pressor response in absence of increased efferent renal sympathetic nerve activity. Losartan effectively blocked responses to intravenous or intracerebroventricular angiotensin II. Intracerebroventricular administration of furosemide produced no changes in mean arterial pressure, heart rate or efferent renal sympathetic nerve activity. It is concluded that intravenous administration of furosemide elicits an immediate increase in efferent renal sympathetic nerve activity via a renal mechanism independent of angiotensin II. Intracerebroventricular furosemide has no effect on central nervous control of mean arterial pressure, heart rate or efferent renal sympathetic nerve activity.     

5／6肾切除致慢性肾衰诱发左室心衰大鼠模型的病理生理

目的研究5／6肾切除引起慢性肾衰诱发左室心衰大鼠模型的病理生理机制。方法雄性SD大鼠经“两次手术切除法”行5／6肾切除,6周后造成慢性肾衰,8周后诱发左室心衰。试剂盒法测定血清钙、磷、肌酐、尿素氮。Bradford法测定24h尿蛋白量。左心室插管术测定心脏血流动力学指标心率（HR）、左室收缩压（LVSP）、左室舒张压（LVDP）、左室舒张末期压（LVEDP）及左室最大压力上升速度（dp／dtmax）和下降速度（-dp／dtmax）。称重法测定心脏重量参数。病理切片HE染色观测心肌病理情况。结果与假手术组相比,除血清钙水平外,病理组大鼠各项指标均比假手术组明显升高,表明慢性肾衰造模成功。与假手术组大鼠比较,病理组大鼠LVSP下降,LVDP和LVEDP均上升。病理组心脏重量参数均比假手术组升高。提示左室舒张和收缩（主要是舒张）功能损伤,发生左室心衰和左室心肌肥厚重构。结论5／6肾切除慢性肾衰诱发的大鼠左室心衰,病理生理学特点是左室舒张和收缩（主要是舒张）功能衰竭,和左室心肌肥厚重构。     

雷米普利对兔心肌梗死后心室肌短暂外向钾电流变化的影响

目的探讨血管紧张素转化酶抑制剂雷米普利对兔心肌梗死后室性心律失常发生的影响及其可能机制。方法将24只家兔完全随机分为假手术组、心肌梗死组和雷米普利组,每组8只。3组均在无菌条件下开胸,其中心肌梗死组和雷米普利组分别结扎左冠状动脉前降支。雷米普利组术后第2天给予雷米普利1mg／（kg·d）灌胃,3组均喂养12周。3组家兔分别在心肌梗死前、心肌梗死后12周记录程序刺激诱发的室性心动过速／心室颤动（VT／VF）发生次数,并采用全细胞膜片钳技术记录短暂外向钾电流（Ito）的变化。结果心肌梗死后12周,雷米普利组VT／VF的发生次数明显低于心肌梗死组[（3．0±0．6）比（12．7±1．5）,P〈0．05];假手术组、心肌梗死组和雷米普利组Ito电流密度分别为（8．69±0．57）pA／pF、（4．71±0．43）pA／pF和（7．32±0．68）pA／pF,心肌梗死组显著高于假手术组及雷米普利组（P〈0．05）;雷米普利组与假手术组比较差异无统计学意义（P〉0．05）。结论长期服用雷米普利可明显降低家兔心肌梗死后VT／VF的发生,其机制可能与抑制家兔心肌梗死后It0有关。     

Chronic infusion of lisinopril into hypothalamic paraventricular nucleus modulates cytokines and attenuates oxidative stress in rostral ventrolateral medulla in hypertension

The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play a critical role in the generation and maintenance of sympathetic nerve activity. The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. This study was designed to determine whether inhibition of the angiotensin-converting enzyme (ACE) in the PVN modulates cytokines and attenuates oxidative stress (ROS) in the RVLM, and decreases the blood pressure and sympathetic activity in renovascular hypertensive rats. Renovascular hypertension was induced in male Sprague–Dawley rats by the two-kidney one-clip (2K1C) method. Renovascular hypertensive rats received bilateral PVN infusion with ACE inhibitor lisinopril (LSP, 10 μg/h) or vehicle via osmotic minipump for 4 weeks. Mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma proinflammatory cytokines (PICs) were significantly increased in renovascular hypertensive rats. The renovascular hypertensive rats also had higher levels of ACE in the PVN, and lower level of interleukin-10 (IL-10) in the RVLM. In addition, the levels of PICs, the chemokine MCP-1, the subunit of NAD(P)H oxidase (gp91^phox) and ROS in the RVLM were increased in hypertensive rats. PVN treatment with LSP attenuated those changes occurring in renovascular hypertensive rats. Our findings suggest that the beneficial effects of ACE inhibition in the PVN in renovascular hypertension are partly due to modulation cytokines and attenuation oxidative stress in the RVLM.     

辛伐他汀干预对急性心肌梗死大鼠ERK1／2信号通路及心室重塑的影响

目的：观察辛伐他汀对急性心肌梗死大鼠心功能、心室肌Ⅰ、Ⅲ型胶原含量变化、心脏细胞外信号调控蛋白激酶1/2（ERK1/2）和p-ERK1/2的影响。方法：20只建模后24h存活的雄性Wistar心肌梗死（AMI）大鼠,随机分为AMI（A）组,辛伐他汀（S）组[20mg/（kg.d）],每组10只,另设假手术（C）组（n=6）,手术方法同模型组,但不结扎冠状动脉。术后8周测定心功能和血流动力学参数。处死后测定左室重量指数（left ventricular weight index,LVWI）;Western blot法检测ERK1/2和p-ERK1/2的表达。结果：辛伐他汀组与AMI组比较心肌梗死面积差异无统计学意义（P〉0.05）;左心室截面直径、面积和左心室容积差异无统计学意义（P〉0.05）;LVW、LVW/BW和LVEDP显著降低（P〈0.01）,±dp/dt/LVSP绝对值升高（P〈0.01）。辛伐他汀组与AMI组相比左心室非梗死区Ⅰ型和Ⅲ型胶原含量和ERK1/2磷酸化水平显著降低（P〈0.01）,左心室非梗死区Ⅰ型、Ⅲ型胶原含量和心脏组织内ERK1/2磷酸化水平均呈显著正相关（r分别为0.916和0.983,P〈0.01）。结论：辛伐他汀能有效抑制AMI左心室非梗死区Ⅰ、Ⅲ型胶原的产生以及缓解大鼠AMI后心室重构、改善心功能。这种作用可能与抑制心脏内ERK1/2磷酸化水平有关。