本文選題：曲美他嗪 + 心衰大鼠�。� 參考：《山東大學(xué)》2014年碩士論文

【摘要】：目的 觀察曲美他嗪對心衰大鼠一般情況及心功能的影響以進(jìn)一步明確該藥物對心力衰竭的治療作用,測定該藥物對心衰大鼠血清IL-12和IL-18水平的影響,探討曲美他嗪抗心衰作用的機(jī)制。 方法 將健康清潔級Wistar雄性大鼠50只,隨機(jī)分成假手術(shù)組(SH組)和手術(shù)組,其中SH組10只,剩余40只為手術(shù)組。手術(shù)組大鼠分為心衰對照組(CHF-C組)和心衰曲美他嗪干預(yù)組(CHF-S組),進(jìn)行腹腔麻醉(3%水合氯醛),沿腹腔中線進(jìn)行切口,之后將腹主動脈從腎動脈上方游離出來,用7號針頭與腹主動脈綁定結(jié)扎,然后對腹腔進(jìn)行縫合手術(shù),結(jié)扎誘導(dǎo)大鼠心衰手術(shù)完成。SH組大鼠行手術(shù)中除不結(jié)扎外,其余與手術(shù)組相同處理過程。手術(shù)組大鼠正常喂養(yǎng)并觀察其水腫、氣喘、飲食狀況、有無紫紺、活動量情況等一般情況。喂養(yǎng)4W后,如符合心衰表現(xiàn),行彩超檢查,選擇心衰模型標(biāo)準(zhǔn)大鼠。給藥方法采用CHF-S組大鼠每天按曲美他嗪1Omg/kg灌胃,而CHF-C組和SH組大鼠灌胃同等量生理鹽水,給藥4W。之后所有各組大鼠麻醉,從心室內(nèi)取血液離心后取上清液保存,用酶聯(lián)免疫吸附法(ELISA)測定IL-18, IL-12.動物處死后取心臟,計(jì)算左心室重量指數(shù)(左心室／大鼠重量)。 結(jié)果 1.給藥后血流動力學(xué)比較：各組大鼠行心臟彩超檢查,記錄左心室舒張期內(nèi)徑(LVDd)、左心室收縮期內(nèi)徑(LVDs)、短軸縮短率(FS)、左室射血分?jǐn)?shù)(EF)。結(jié)果顯示,CHF-C組左心室舒張期內(nèi)徑(LVDd)、左心室收縮期內(nèi)徑(LVDs)值最高,射血分?jǐn)?shù)(EF)、短軸縮短率(FS)值最低,與其他各組比,其組間的差別有統(tǒng)計(jì)學(xué)意義(P0.05)。SH組組左心室舒張期內(nèi)徑(LVDd)、左心室收縮期內(nèi)徑(LVDs)值最低,射血分?jǐn)?shù)(EF)、短軸縮短率(FS)值最高,與其他各組比,其組間的差別有統(tǒng)計(jì)學(xué)意義(P0.05)。CHF-S組左心室舒張期內(nèi)徑(LVDd)、左心室收縮期內(nèi)徑(LVDs)、射血分?jǐn)?shù)(EF)、短軸縮短率(FS)值比較,組間差別無統(tǒng)計(jì)學(xué)意義(P0.05)。 2.給藥后各組心室重塑比較：與假手術(shù)組相比,模型組及曲美他嗪干預(yù)組體重均減輕(P0.05,P0.05)；曲美他嗪干預(yù)組體重均較模型組增高(P0.05)；左室質(zhì)量重量3組直接無統(tǒng)計(jì)學(xué)意義,模型組及曲美他嗪干預(yù)組左室重量均低于假手術(shù)組；左室質(zhì)量指數(shù)LVE/BW曲美他嗪干預(yù)組介于假手術(shù)組與模型組之間,與假手術(shù)相比,模型組及曲美他嗪干預(yù)組均降低,差異有統(tǒng)計(jì)學(xué)意義(P0.01,P0.01)；曲美他嗪干預(yù)組LVE/BW與模型組相比,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。 3.給藥后各組大鼠心肌組織比較：通過HE染色,在倒置顯微鏡下觀察。結(jié)果表明：SH組：心肌細(xì)胞大小、結(jié)構(gòu)正常,排列規(guī)則；胞質(zhì)染色均勻,細(xì)胞核數(shù)量、染色正常；細(xì)胞間質(zhì)少；CHF-C組：心肌細(xì)胞腫脹,界限不清,細(xì)胞核數(shù)量少,染色淺；胞質(zhì)局部淡染、空化；心肌纖維間充滿大量紅細(xì)胞或中性粒細(xì)胞浸潤；CHF-S組的形態(tài)變化較CHF-C組均有不同程度改善,細(xì)胞略腫脹,間隙略增大,少量血細(xì)胞浸潤。 4.TMZ給藥后各組大鼠心細(xì)胞橫截面積比較：應(yīng)用圖像分析軟件IPP6.0測量3組大鼠心肌組織左室橫截面病理切片細(xì)胞面積。各組大鼠心肌細(xì)胞橫截面積(cross-sectional area, CSA),各組大鼠心肌細(xì)胞CSA從大到小依次為模型組、曲美他嗪組、假手術(shù)組,假手術(shù)組與模型組比較,差異有統(tǒng)計(jì)學(xué)意義(P0.01)；與模型組比較,曲美他嗪組CSA顯著縮小,差異有統(tǒng)計(jì)學(xué)意義(P0.01)；與假手術(shù)組比較,曲美他嗪組CSA縮小,但無統(tǒng)計(jì)學(xué)意義。 5實(shí)驗(yàn)后各組間IL-12與IL-18的比較顯示：假手術(shù)組的IL-12值最低,與模型組及曲美他嗪干預(yù)組比,差異有統(tǒng)計(jì)學(xué)意義(P0.01,P0.05)。與模型組比較,與曲美他嗪干預(yù)組比,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。各組間IL-18比較,模型組的IL-18值最高,與曲美他嗪干預(yù)組比,差異有統(tǒng)計(jì)學(xué)意義(P0.01)。假手術(shù)組IL-18值最低,與與模型組及曲美他嗪干預(yù)組比,差異有統(tǒng)計(jì)學(xué)意義(P0.01,P0.05)。 結(jié)論 1.心衰大鼠中IL-18的變化規(guī)律,提示IL-12和IL-18水平的升高,促進(jìn)了心衰的發(fā)展。 2.曲美他嗪能夠通過降低IL-12和IL-18水平,進(jìn)而顯著改善了心衰大鼠的癥狀,接下來仍需大規(guī)模臨床實(shí)驗(yàn)給予循證學(xué)證據(jù)。
[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.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R541.6

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