| 巩 亮,王晓春,焦 阳,姜顺涛,杨光磊.氯沙坦联合螺内酯对预N-硝基-L-精氨酸甲酯诱导高血压模型大鼠肾脏纤维化及心室重塑的影响[J].现代生物医学进展英文版,2022,(5):822-826. |
| 氯沙坦联合螺内酯对预N-硝基-L-精氨酸甲酯诱导高血压模型大鼠肾脏纤维化及心室重塑的影响 |
| Effects of Losartan Combined with Spironolactone on Renal Fibrosis and Ventricular Remodeling in Hypertensive Rats Induced by N-nitro-L-arginine Methyl Ester |
| Received:May 07, 2021 Revised:May 31, 2021 |
| DOI：10.13241/j.cnki.pmb.2022.05.005 |
| 中文关键词: 氯沙坦 螺内酯 L-NAME 高血压 心脏重塑 肾脏纤维化 |
| 英文关键词: Losartan Spironolactone L-NAME Hypertension Heart remodeling Renal fibrosis |
| 基金项目:贵州省科技厅基金项目（黔科合基础[2016]1173） |
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| 中文摘要: |
| 摘要 目的：探讨氯沙坦联合螺内酯对预N-硝基-L-精氨酸甲酯（N'-nitro-L-arginine-methylesterhydrochloride，L-NAME）诱导高血压模型大鼠肾脏纤维化及心室重塑的影响。方法：选择8周龄Wistar大鼠为研究对象，通过给予0.1 %的L-NAME饮用水诱导高血压模型。将大鼠根据随机数字表法分为三组：对照组，诱导组和联合治疗组。通过超声心动图比较室间隔厚度和左心室后壁厚度。CODATM8无创血压系统监测大鼠心脏功能。通过蛋白印迹分析大鼠肾切片中I型胶原、III型胶原和CTGF的蛋白表达。Masson的三色染色评估肾脏组织胶原含量沉积。通过RT-PCR分析大鼠心脏肥大标志物和转录因子心房利钠肽（Atrial natriuretic peptide，ANP）和脑利钠肽（Brain natriuretic peptide，BNP）的表达。通过免疫组化和免疫比浊法分析大鼠肾小球硬化指数和白蛋白尿。结果：模型组较对照组大鼠室间隔厚度和左心室后壁厚度、MAP和心脏/体重比、I型胶原、III型胶原和CTGF的蛋白表达、ANP和BNP的mRNA表达、肾小球硬化指数和白蛋白尿以及SMA和TGF-β1的蛋白表达均显著增加，FS显著降低（P<0.05），联合治疗组较模型组室间隔厚度和左心室后壁厚度、MAP和心脏/体重比、I型胶原、III型胶原和CTGF的蛋白表达、ANP和BNP的mRNA表达、肾小球硬化指数和白蛋白尿以及SMA和TGF-β1的蛋白表达均显著降低，FS显著增加（P<0.05）。结论：氯沙坦联合螺内酯可减轻L-NAME诱导的高血压大鼠模型中心脏重塑和肾脏纤维化的发生。 |
| 英文摘要: |
| ABSTRACT Objective: To explore the effect of losartan combined with spironolactone on N'-nitro-L-arginine-methylesterhydrochloride (L-NAME) induced renal fibrosis and ventricular remodeling in hypertensive rats influences. Methods: Eight-week-old Wistar rats were selected as the research object, and the hypertension model was induced by giving 0.1% L-NAME drinking water. The rats were divided into three groups according to the random number table: the control group, the induction group and the combined treatment group. The thickness of the interventricular septum and the thickness of the posterior wall of the left ventricle were compared by echocardiography. CODATM8 non-invasive blood pressure system monitors rat heart function. The protein expression of type I collagen, type III collagen and CTGF in rat kidney sections was analyzed by Western blot. Masson's trichromatic staining assesses the deposition of collagen content in kidney tissue. The expressions of rat cardiac hypertrophy markers and transcription factors Atrial natriuretic peptide (ANP) and Brain natriuretic peptide(BNP) were analyzed by RT-PCR. Analyze rat glomerulosclerosis index and albuminuria by immunohistochemistry and immunoturbidimetry. Results: Compared with the control group, the thickness of the ventricular septum and the thickness of the posterior wall of the left ventricle, the MAP and heart/weight ratio, the protein expression of type I collagen, type III collagen and CTGF, the mRNA expression of ANP and BNP, the glomerulosclerosis index and the expression of the model group were compared with those of the control group. Albuminuria and the protein expression of SMA and TGF-β1 all increased significantly, while FS was significantly reduced(P<0.05); The combined treatment group compared the thickness of the ventricular septum and the thickness of the left ventricular posterior wall, the MAP and heart/weight ratio, the protein expression of type I collagen, type III collagen and CTGF, the mRNA expression of ANP and BNP, the glomerular sclerosis index and the whiteness of the model group. Proteinuria and the protein expression of SMA and TGF-β1 were significantly reduced, while FS increased significantly(P<0.05). Conclusion: Losartan combined with spironolactone can reduce the occurrence of cardiac remodeling and renal fibrosis in the L-NAME-induced hypertensive rat model. |
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