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右旋美托咪啶在膿毒血癥繼發(fā)性肺損傷中的作用及可能機(jī)制

發(fā)布時(shí)間:2018-12-31 17:27
【摘要】:目的觀察右旋美托咪啶(DEX)預(yù)處理對(duì)不同發(fā)展階段的敗血癥的影響及其可能機(jī)制。 實(shí)驗(yàn)方法采用忙腸結(jié)扎穿孔法建立敗血癥模型,149只SD大鼠隨機(jī)分配入空白對(duì)照組22只(無(wú)任何處理)、假手術(shù)組22只(剖腹探查和腸系膜血管盲腸支分離并放置引流條)、手術(shù)組35只(剖腹探查后腸系膜血管盲腸支分離,盲腸結(jié)扎穿孔術(shù)后放置引流條)、右旋美托咪啶預(yù)處理組35只(麻醉10min后腹腔注射右美lOug/kg,之后手術(shù)處理)、及阿替美唑拮抗組35只(麻醉時(shí)腹腔注射阿替美唑250ug/kg,之后處理同右美組),并觀察術(shù)后24h內(nèi)存活率、測(cè)量肛溫、疾病嚴(yán)重程度評(píng)分(空白和假手術(shù)組各10只,其余組各15只),并于術(shù)后4h、8h、12h、24h處死大鼠(空白和假手術(shù)組每個(gè)時(shí)間點(diǎn)3只,其余組5只),取左室血測(cè)血?dú)?取肺組織行HE染色做病理評(píng)分,及肺小窩蛋白westernblot法分析其隨疾病進(jìn)展的表達(dá)變化。統(tǒng)計(jì)學(xué)處理采用SPSS22.0軟件,所有測(cè)量值用均數(shù)±標(biāo)準(zhǔn)差(M±SD)表示,體溫及疾病嚴(yán)重程度評(píng)分組內(nèi)比較采用復(fù)合效應(yīng)線性模型分析,組間比較采用完全隨機(jī)設(shè)計(jì)多個(gè)組兩兩比較(LSD)方差分析。方差一致性檢驗(yàn)采用Levene或Bartlet's檢驗(yàn)。組間生存率資料用log-rank口2檢驗(yàn),生存曲線用Kaplan Meier分析。差異顯著性水平設(shè)為雙尾a=0.05。 結(jié)果 (1)右美預(yù)處理能顯著提高敗血癥大鼠24小時(shí)存活率(40%vs.C組20%,P0.05),阿替美唑(AMZ)對(duì)DEX的這一保護(hù)作用無(wú)顯著拮抗(46.7%,P0.05,vs. CD)。 (2)右美預(yù)處理能顯著抑制敗血癥引起的體溫升高、肺部病理改變(P0.05, vs. C),未顯著改善疾病癥狀評(píng)分(P0.05, vs. C);阿替美唑顯著拮抗其抗炎性細(xì)胞浸潤(rùn)作用(P0.05, vs.CD),改善肺部水腫(P0.05,vs.CD),提高疾病癥狀評(píng)分(P0.05,vs.CD)。 (3)敗血癥能顯著影響小窩蛋白表達(dá)規(guī)律并下調(diào)其表達(dá)(P0.05,vs.S/CT),右美預(yù)處理能抑制敗血癥引起的表達(dá)規(guī)律改變(P0.05,vs. C)并上調(diào)其表達(dá)(P0.05,vs.C),阿替美唑顯著拮抗右美上調(diào)小窩蛋白的作用(P0.05,vs. CD),但并未抑制其對(duì)小窩蛋白表達(dá)規(guī)律的保護(hù)作用。 結(jié)論右美預(yù)處理能顯著降低膿毒血癥的死亡率和肺損傷,這可能部分通過(guò)激活α2腎上腺素受體和咪唑林受體維持小窩蛋白的表達(dá)起作用。
[Abstract]:Objective to observe the effect of dexmetidine (DEX) preconditioning on septicemia in different stages and its possible mechanism. Methods the septicemia model was established by busy intestinal ligation and perforation. 149 SD rats were randomly assigned to the blank control group (22 rats without any treatment) and the sham operation group (22 rats underwent laparotomy and mesenteric caecum branch separation and placed drainage strips). 35 rats in operation group were treated with caecum branches of mesenteric vessels after laparotomy, drainage strips were placed after cecal ligation and perforation, and 35 rats in dexmetidine preconditioning group (after intraperitoneal injection of dexamethasone after anaesthesia 10min). And altimezole antagonist group (35 rats were treated with altimetrazole 250 g / kg intraperitoneally during anesthesia and treated with the same right side group), and the survival rate, anal temperature and disease severity score were observed within 24 hours after operation (10 rats in blank group and 10 in sham operation group). 15 rats in each group were killed at 4 h, 8 h, 12 h and 24 h after operation (3 rats in blank and sham-operation group and 5 rats in other group). Blood gas was measured in left ventricular blood and HE staining was performed in lung tissue for pathological evaluation. And lung fossa protein westernblot method was used to analyze the expression of lung fossa protein with disease progression. SPSS22.0 software was used for statistical analysis, all measurements were expressed by mean 鹵standard deviation (M 鹵SD). The body temperature and disease severity score group were compared by compound effect linear model analysis. (LSD) ANOVA was used to compare two groups of groups with complete random design. Variance consistency test was performed by Levene or Bartlet's test. The survival rate was examined by log-rank 's mouth 2 test and the survival curve was analyzed by Kaplan Meier. The significant level of the difference was 0. 05. Results (1) the 24 hour survival rate of septicemia rats was significantly increased by dexamethasone preconditioning (40%vs.C group 20: P0.05), but the protective effect of altimezole (AMZ) on DEX was not significantly antagonized (46.7% P 0.05). Vs. CD). (2) dexamethasone pretreatment could significantly inhibit the hyperthermia induced by septicemia and pulmonary pathological changes (P0.05, vs. C), did not significantly improve the symptom score (P0.05, vs. C);). Altimezole significantly antagonized its anti-inflammatory cell infiltration (P0.05, vs.CD), improved pulmonary edema (P0.05vs.CD) and increased the disease symptom score (P0.05vs.CD). (3) septicemia could significantly affect the expression of fossa protein and down-regulate its expression (P0.05vs.SrCT). Right preconditioning could inhibit the change of expression pattern (P0.05V 路C) and up-regulate its expression (P0.05). Vs.C, Atemezole significantly antagonized the up-regulation of fossa protein (P0.05V 路CD), but did not inhibit its protective effect on the expression of fossa protein. Conclusion dexamethasone preconditioning can significantly reduce mortality and lung injury of sepsis, which may partly play a role by activating 偽 2-adrenoceptor and midazoline receptor to maintain the expression of fossa protein.
【學(xué)位授予單位】:中南大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2014
【分類(lèi)號(hào)】:R614

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 農(nóng)麗丹;鄧春玉;鄺素娟;張光燕;崔建修;;右美托咪定抑制五羥色胺誘導(dǎo)的人離體肺內(nèi)小動(dòng)脈收縮[J];南方醫(yī)科大學(xué)學(xué)報(bào);2014年03期

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