螺内酯对盐诱导高血压大鼠心肌间质纤维化及ⅠL-17A表达的作用研究

发布时间：2018-04-16 12:09

本文选题：盐诱导高血压 + 左心室重构　；参考：《广西医科大学》2017年硕士论文

【摘要】：目的探讨螺内酯对盐诱导高血压大鼠左室心肌间质纤维化及白介素17A(IL-17A)的影响。方法80只5周龄Wistar大鼠,随机分为正常对照组、2%氯化钠组、3%氯化钠组、2%氯化钠干预组和3%氯化钠干预组每组16只;正常对照组、2%氯化钠组和3%氯化钠组分别给予蒸馏水、2%和3%氯化钠饲养10周,2%氯化钠干预组、3%氯化钠干预组分别用2%和3%氯化钠饲养5周后,给予螺内酯20mg/(g·d)灌胃再饲养5周;每周尾袖法测动脉血压1次,饲养10周后全部麻醉并处死,抽腹主动脉血和留取左心室心肌组织待检测,HE染色观察左心室心肌细胞形态,Masson染色观察心肌胶原纤维并计算胶原容积分数(CVF),免疫组化、酶联免疫吸附法(ELISA)分别检测IL-17A、TNF-α、MMP-9、TGF-β1在心肌组织和血浆中的表达水平。结果(1)全部大鼠饲养10周后,死亡8只,死亡率10%(8/80),成模51只,成模率79.69%(51/64),其中2%氯化钠组成模率75%(12/16),死亡率12.5%(2/16),3%氯化钠组成模率81.3%(13/16),死亡率12.5%(2/16),2%氯化钠+螺内酯组成模率87.5%(14/16),死亡率12.5%(2/16)和3%干氯化钠+螺内酯组成模率75%(12/16),死亡率12.5%(2/16)。(2)与正常对照组相比,2%氯化钠组、3%氯化钠组、2%氯化钠+螺内酯组和3%氯化钠+螺内酯组大鼠的平均收缩压及平均舒张压均显著增高(均P0.05),与2%和3%氯化钠组相比,两螺内酯组的平均收缩压明显降低(均P0.05);但2%和3%氯化钠组之间、两螺内酯组之间收缩压水平无差异(P0.05)。(3)与正常对照组相比,2%和3%氯化钠组大鼠的左室内径均显著增大(均P0.05);与2%和3%氯化钠组相比,螺内酯干预5周后两螺内酯组的平均左室内径均显著下降(均P0.01);但2%和3%氯化钠组之间、两螺内酯组之间差别不明显(P0.05)。(4)与正常对照组相比,2%和3%氯化钠组大鼠心肌和血浆中IL-17A、TNF-α、MMP-9和TGF-β1的水平显著增高(均P0.05),2%和3%氯化钠干预组大鼠的血浆和心肌组织中IL-17A、TNF-α、MMP-9和TGF-β1的水平显著下降(均P0.05),但2%和3%氯化钠组间及2%和3%氯化钠+螺内酯组间上述指标均无明显差异。(5)与正常对照组相比,2%和3%氯化钠组大鼠的CVF(P0.05)均显著增高;但螺内脂干预5周后2%和3%氯化钠组CVF均明显降低,但2%氯化钠+螺内酯组较3%氯化钠+螺内酯组降低更明显(P0.05)(6)相关分析发现:IL-17A与TNF-α、MMP-9、TGF-β1表达呈正相关(r=0.5、0.4、0.5,均P0.05);CVF与IL-17A、TNF-α、MMP-9、TGF-β1均呈正相关(r=0.4、0.6、0.7、0.8;均P0.01)。(7)心肌组织HE和Masson染色:成模大鼠心肌细胞增生肥大、灶性溶解,纤维组织增多;螺内酯干预组大鼠心肌细胞增生、肥大、灶性溶解程度较轻,纤维组织显著减少。结论盐诱导高血压大鼠的IL-17A表达明显增高,与TNF-α、MMP-9、和TGF-β1表达呈正相关;螺内酯干预后IL-17A、TNF-α、MMP-9、TGF-β1和CVF均显著降低;提示螺内酯可能通过调控IL-17A、TNF-α、MMP-9和TGF-β1等因子的表达而逆转左室间质纤维化。
[Abstract]:Objective to investigate the effect of spironolactone on left ventricular interstitial fibrosis and interleukin 17 A (IL 17 A) induced by salt in hypertensive rats.Methods 80 5-week-old Wistar rats were randomly divided into 2% sodium chloride group (n = 16) and 3% sodium chloride group (n = 16).Normal control group (2% sodium chloride group) and 3% sodium chloride group (3% sodium chloride group) were fed with distilled water 2% and 3% sodium chloride for 10 weeks respectively. The 3% sodium chloride intervention group was fed with 2% and 3% sodium chloride for 5 weeks, and then fed with spironolactone 20mg/(g for 5 weeks.Arterial blood pressure was measured by cuff method once a week. After feeding for 10 weeks, all patients were anesthetized and executed.Extraction of abdominal aorta blood and left ventricular myocardial tissue to be detected by HE staining to observe left ventricular cardiomyocytes morphology and Masson staining to observe myocardial collagen fiber and calculate collagen volume fraction CVFFI, immunohistochemistry,Enzyme linked immunosorbent assay (Elisa) was used to detect the expression of IL-17An TNF- 伪-伪 -MMP-9 and TGF- 尾 1 in myocardium and plasma.Results 1) after 10 weeks of feeding, 8 rats died, and the mortality rate was 10% / 80%, 51 rats were modelled.79.69% 51 / 64%, of which 2% sodium chloride composition is 75 / 12 / 16%, mortality rate is 12.55% / 2 / 16%, sodium chloride composition rate is 81.33 / 16%, mortality rate is 12.55% / 21% / 2% sodium chloride spironolactone composition module rate is 87.555% 14 / 16%, mortality rate 12.555% / 216%) and 3% dry sodium chloride spironolactone composition module rate 75 / 12 / 16%, mortality rate 12.555% / 22%.The mean systolic blood pressure and mean diastolic pressure of rats in 2% sodium chloride group and 3% sodium chloride spironolactone group were significantly higher than those in 2% sodium chloride group and 3% sodium chloride group (all P 0.05, compared with 2% and 3% sodium chloride groups).The mean systolic blood pressure of the two spironolactone groups decreased significantly (both P0.05N; but between the 2% and 3% sodium chloride groups),There was no difference in systolic blood pressure level between the two spironolactone groups (P 0.05).) the left ventricular diameter of rats in 2% and 3% sodium chloride groups increased significantly compared with the normal control group (P0.05%; compared with 2% and 3% sodium chloride group, respectively), the left ventricular diameter of the rats in the 2% and 3% sodium chloride groups was significantly higher than that in the control group (P < 0.05).The mean left ventricular diameter in the two spironolactone groups decreased significantly after 5 weeks of intervention (all P 0.01), but between the 2% and 3% sodium chloride groups,The levels of IL-17AnTNF- 伪, MMP-9 and TGF- 尾 1 in myocardium and plasma of rats in the 2% and 3% sodium chloride groups were significantly higher than those in the control group (both P0.05% and 3% sodium chloride intervention group) (both P0.05% and 3% sodium chloride intervention group). The levels of IL-17 ANF- 伪 TNF- 伪 MMP-9 and TGF- 尾 1 in the plasma and myocardium of the rats in the intervention group were significantly higher than those in the control group (both P0.05% and 3% sodium chloride group).The level of TGF- 尾 _ 1 decreased significantly (all P 0.05, but there was no significant difference between 2% and 3% sodium chloride groups and 2% and 3% sodium chloride spironolactone groups.) compared with the normal control group, the CVFFN P0.05 of rats in 2% and 3% sodium chloride groups were significantly higher than those in the control group.However, the CVF of 2% and 3% sodium chloride groups decreased significantly after 5 weeks of intraspirolide intervention.In the group treated with spironolactone, the cardiac myocytes proliferated, hypertrophy, the degree of focal dissolving was light, and the fibrous tissue decreased significantly.Conclusion the expression of IL-17A in salt-induced hypertensive rats was significantly increased, which was positively correlated with the expression of TNF- 伪 -MMP-9 and TGF- 尾 _ 1, and decreased significantly after the intervention of spironolactone, suggesting that spironolactone might reverse the left ventricular interstitial fibrosis by regulating the expression of IL-17A- TNF- 伪 MMP-9 and TGF- 尾 _ 1.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R544.1;R542.2

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