曲美他嗪对心衰大鼠IL-12和IL-18的影响

发布时间：2018-07-01 11:03

本文选题：曲美他嗪 + 心衰大鼠　；参考：《山东大学》2014年硕士论文

【摘要】：目的观察曲美他嗪对心衰大鼠一般情况及心功能的影响以进一步明确该药物对心力衰竭的治疗作用,测定该药物对心衰大鼠血清IL-12和IL-18水平的影响,探讨曲美他嗪抗心衰作用的机制。方法将健康清洁级Wistar雄性大鼠50只,随机分成假手术组(SH组)和手术组,其中SH组10只,剩余40只为手术组。手术组大鼠分为心衰对照组(CHF-C组)和心衰曲美他嗪干预组(CHF-S组),进行腹腔麻醉(3%水合氯醛),沿腹腔中线进行切口,之后将腹主动脉从肾动脉上方游离出来,用7号针头与腹主动脉绑定结扎,然后对腹腔进行缝合手术,结扎诱导大鼠心衰手术完成。SH组大鼠行手术中除不结扎外,其余与手术组相同处理过程。手术组大鼠正常喂养并观察其水肿、气喘、饮食状况、有无紫绀、活动量情况等一般情况。喂养4W后,如符合心衰表现,行彩超检查,选择心衰模型标准大鼠。给药方法采用CHF-S组大鼠每天按曲美他嗪1Omg/kg灌胃,而CHF-C组和SH组大鼠灌胃同等量生理盐水,给药4W。之后所有各组大鼠麻醉,从心室内取血液离心后取上清液保存,用酶联免疫吸附法(ELISA)测定IL-18, IL-12.动物处死后取心脏,计算左心室重量指数(左心室／大鼠重量)。结果 1.给药后血流动力学比较：各组大鼠行心脏彩超检查,记录左心室舒张期内径(LVDd)、左心室收缩期内径(LVDs)、短轴缩短率(FS)、左室射血分数(EF)。结果显示,CHF-C组左心室舒张期内径(LVDd)、左心室收缩期内径(LVDs)值最高,射血分数(EF)、短轴缩短率(FS)值最低,与其他各组比,其组间的差别有统计学意义(P0.05)。SH组组左心室舒张期内径(LVDd)、左心室收缩期内径(LVDs)值最低,射血分数(EF)、短轴缩短率(FS)值最高,与其他各组比,其组间的差别有统计学意义(P0.05)。CHF-S组左心室舒张期内径(LVDd)、左心室收缩期内径(LVDs)、射血分数(EF)、短轴缩短率(FS)值比较,组间差别无统计学意义(P0.05)。 2.给药后各组心室重塑比较：与假手术组相比,模型组及曲美他嗪干预组体重均减轻(P0.05,P0.05)；曲美他嗪干预组体重均较模型组增高(P0.05)；左室质量重量3组直接无统计学意义,模型组及曲美他嗪干预组左室重量均低于假手术组；左室质量指数LVE/BW曲美他嗪干预组介于假手术组与模型组之间,与假手术相比,模型组及曲美他嗪干预组均降低,差异有统计学意义(P0.01,P0.01)；曲美他嗪干预组LVE/BW与模型组相比,差异有统计学意义(P0.05)。 3.给药后各组大鼠心肌组织比较：通过HE染色,在倒置显微镜下观察。结果表明：SH组：心肌细胞大小、结构正常,排列规则；胞质染色均匀,细胞核数量、染色正常；细胞间质少；CHF-C组：心肌细胞肿胀,界限不清,细胞核数量少,染色浅；胞质局部淡染、空化；心肌纤维间充满大量红细胞或中性粒细胞浸润；CHF-S组的形态变化较CHF-C组均有不同程度改善,细胞略肿胀,间隙略增大,少量血细胞浸润。 4.TMZ给药后各组大鼠心细胞横截面积比较：应用图像分析软件IPP6.0测量3组大鼠心肌组织左室横截面病理切片细胞面积。各组大鼠心肌细胞横截面积(cross-sectional area, CSA),各组大鼠心肌细胞CSA从大到小依次为模型组、曲美他嗪组、假手术组,假手术组与模型组比较,差异有统计学意义(P0.01)；与模型组比较,曲美他嗪组CSA显著缩小,差异有统计学意义(P0.01)；与假手术组比较,曲美他嗪组CSA缩小,但无统计学意义。 5实验后各组间IL-12与IL-18的比较显示：假手术组的IL-12值最低,与模型组及曲美他嗪干预组比,差异有统计学意义(P0.01,P0.05)。与模型组比较,与曲美他嗪干预组比,差异有统计学意义(P0.05)。各组间IL-18比较,模型组的IL-18值最高,与曲美他嗪干预组比,差异有统计学意义(P0.01)。假手术组IL-18值最低,与与模型组及曲美他嗪干预组比,差异有统计学意义(P0.01,P0.05)。结论 1.心衰大鼠中IL-18的变化规律,提示IL-12和IL-18水平的升高,促进了心衰的发展。 2.曲美他嗪能够通过降低IL-12和IL-18水平,进而显著改善了心衰大鼠的症状,接下来仍需大规模临床实验给予循证学证据。
[Abstract]:objective
To observe the effect of trimetazidine on the general condition and cardiac function of rats with heart failure in order to further clarify the therapeutic effect of the drug on heart failure, determine the effect of the drug on the serum levels of IL-12 and IL-18 in rats with heart failure, and explore the mechanism of the anti heart failure of Trimetazidine.
Method
50 healthy and clean Wistar male rats were randomly divided into sham operation group (group SH) and operation group, of which 10 were in group SH and 40 were in operation group. The operation group was divided into heart failure control group (group CHF-C) and heart failure triazine intervention group (group CHF-S), abdominal anesthesia (3% hydrochloral chloral), incision along the midline of abdominal cavity, and abdominal aorta Free from the renal artery, ligation of the abdominal aorta with No. 7 needle and abdominal aorta, and then suture the abdominal cavity, ligation of the rat heart failure operation to complete the.SH group, the rest of the operation was the same as the operation group. The operation group was normally fed and observed their edema, asthma, diet and cyanosis. After feeding 4W, after feeding the heart failure, the color Doppler ultrasonography was used to select the standard rat model of heart failure. The method of administration of the CHF-S group was administered by trimetazidine 1Omg/kg every day, while the CHF-C and SH rats were given the same amount of normal saline, and all the rats were anesthetized and centrifuged from the ventricle after 4W.. After taking the supernatant, the IL-18 was measured by ELISA. The heart was taken after the death of the IL-12. animals, and the left ventricular mass index (left ventricular / rat weight) was calculated.
Result
1. after administration, hemodynamic comparison: the left ventricular diastolic diameter (LVDd), the left ventricular systolic diameter (LVDs), the short axis shortening rate (FS) and the left ventricular ejection fraction (EF) were recorded in each group. The results showed that the left ventricular diastolic diameter (LVDd), the left ventricular systolic diameter (LVDs), the ejection fraction (EF), the short axis contraction (EF), and the short axis contraction were found in the CHF-C group. The short rate (FS) was the lowest, and the difference between the groups was statistically significant (P0.05) in the group.SH group, the left ventricular diastolic diameter (LVDd), the left ventricular systolic diameter (LVDs) was the lowest, the ejection fraction (EF), the short axis shortening rate (FS) was the highest, and the difference between the groups was statistically significant (P0.05) the left ventricular diastolic phase of group.CHF-S (P0.05). There was no significant difference in the internal diameter (LVDd), left ventricular systolic diameter (LVDs), ejection fraction (EF) and shortening axis shortening (FS) value between the two groups (P0.05).
2. compared with the sham group, the weight of the model group and the trimetazidine intervention group were all reduced (P0.05, P0.05), and the weight of the trimetazidine intervention group was higher than that of the model group (P0.05); the left ventricular mass weight of the 3 groups had no statistical significance, the left ventricular weight of the model group and the trimetazidine intervention group were lower than the sham group. The left ventricular mass index LVE/BW trimetazidine intervention group was between the sham operation group and the model group, compared with the sham operation, the model group and the trimetazidine intervention group were all lower, the difference was statistically significant (P0.01, P0.01), and the difference was statistically significant (P0.05) compared with the model group of the trimetazidine intervention group (LVE/BW).
3. the myocardium tissue of rats in each group was compared by HE staining and observed under the inverted microscope. The results showed that group SH: the size of the myocardial cells, the structure of the normal structure, the regular arrangement, the homogeneous cytoplasm staining, the number of nuclei, the normal staining of the cell, the CHF-C group: the myocyte swelling, the indistinct boundary, the small number of nuclei and shallow staining; The cytoplasm was partially dyed and cavitation; a large number of red cells or neutrophil infiltration were filled between the myocardial fibers, and the morphological changes of CHF-S group were improved in different degrees compared with that of the CHF-C group. The cells were slightly swelling, the gap was slightly enlarged and a small amount of blood cells were infiltrated.
The cross section area of cardiac cells in each group was compared with 4.TMZ after administration: IPP6.0 was used to measure the area of left ventricular cross section of myocardial tissue in 3 groups of rats by image analysis software. The cross section area of myocardial cells (cross-sectional area, CSA) in each group of rats. The CSA of cardiac myocytes in each group was in the order of the model group, the Trimetazine group, and the false hand. The difference between the sham operation group and the model group was statistically significant (P0.01). Compared with the model group, the CSA of trimetazidine group was significantly reduced and the difference was statistically significant (P0.01). Compared with the sham operation group, the CSA of trimetazidine group was reduced, but there was no statistical significance.
After 5 experiments, the comparison of IL-12 and IL-18 showed that the IL-12 value of the sham operation group was the lowest, and the difference was statistically significant (P0.01, P0.05) compared with the model group and the Trimetazine intervention group (P0.01, P0.05). Compared with the model group, the difference was statistically significant (P0.05). The IL-18 value of the model group was the highest, compared with the model group (P0.05). The difference between the model group and the Trimetazine was the highest in the model group, and the Trimetazine in the model group. The difference was statistically significant (P0.01). The IL-18 value of the sham operation group was the lowest, and the difference was statistically significant (P0.01, P0.05) compared with the model group and the Trimetazine intervention group.
conclusion
1. the change of IL-18 in heart failure rats indicates that the increase of IL-12 and IL-18 levels promotes the development of heart failure.
2. trimetazidine can significantly improve the symptoms of heart failure rats by reducing the levels of IL-12 and IL-18, and then still need evidence-based evidence in large-scale clinical trials.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R541.6

【参考文献】