本文關(guān)鍵詞： 一氧化碳 血紅素氧合酶 內(nèi)毒素 肺 腎 炎癥　出處：《河北醫(yī)科大學(xué)》2005年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:腹腔感染所致的感染性休克是一種臨床常見(jiàn)的病理過(guò)程,發(fā)病急驟,并發(fā)癥多,可累及機(jī)體多個(gè)器官,甚至導(dǎo)致多器官功能障礙綜合征(multiple organ dysfunctionsyndrome,MODS)。而肺臟和腎臟是經(jīng)常受累的器官,主要為內(nèi)素素誘導(dǎo)誘導(dǎo)炎癥介質(zhì)失控性釋放,從而引起機(jī)體器官的損傷,但其具體的作用機(jī)制尚未完全明了,氧化應(yīng)激可能是肺和腎損傷的主要機(jī)制之一。已有研究表明,一氧化碳(carbon monoxide,CO)可抑制機(jī)體炎癥因子的產(chǎn)生,對(duì)抗氧自由基損傷,但對(duì)盲腸結(jié)扎穿孔(cecal ligation andpuncture,CLP)導(dǎo)致感染性休克時(shí)肺和腎損傷是否也具有保護(hù)作用尚有待探討。本研究使用CLP 的方法建立感染性休克模型,通過(guò)應(yīng)用血紅素氧合酶(heme oxygenase,HO)誘導(dǎo)劑氯血紅素(Hemin)和抑制劑鋅原卟啉(Zinc protoporphyrin,ZnPP)調(diào)節(jié)HO-1 活性來(lái)控制內(nèi)源性CO 的生成,探討內(nèi)源性CO 對(duì)肺和腎損傷的保護(hù)作用及其可能機(jī)制。 方法:實(shí)驗(yàn)用雄性Sprague Dawley(SD)大鼠,體重200～250 克,隨機(jī)分為四組,每組24 只。(1)假手術(shù)組:腹腔注射25%烏拉坦4mg/kg 麻醉,行腹部正中切口,于盲腸根部穿線而不結(jié)扎,逐層縫合;(2)CLP 組:開(kāi)腹后結(jié)扎盲腸根部,在腸系膜相對(duì)的盲腸漿膜面用18 號(hào)針頭穿刺兩個(gè)孔(相距1 厘米),逐層縫合;(3)CLP+Hemin 組:手術(shù) 前10min 經(jīng)舌下靜脈注射Hemin(10mg/kg),其余操作同CLP 組;(4)CLP+ZnPP 組:手術(shù)前10min 舌下靜脈注射ZnPP(10mg/kg),其余操作同CLP 組。各組分別于模型成立后2h、4h、6h 從右頸靜脈插管至右心房,分離左頸靜脈插管至主動(dòng)脈根部,采集血液分別代表出肺血(Out-going pulmonaryblood,OPB)和入肺血(In-flowing pulmonary blood,IPB),以檢測(cè)其碳氧血紅蛋白(carboxyhemoglobin,COHb)水平,以此代表CO 含量,經(jīng)頸靜脈取血液標(biāo)本后繼續(xù)放血處死動(dòng)物,取肺、腎組織標(biāo)本,將血液標(biāo)本離心后取上清液,將肺、腎組織標(biāo)本制備勻漿,以檢測(cè)血液及肺、腎組織中的超氧化物歧化酶(superoxidedismutase,SOD)活性、丙二醛(malondialdehyde,MDA)含量。另外留取肺、腎組織標(biāo)本,光鏡觀察其病理學(xué)改變,免疫組織化學(xué)染色觀察其HO-1 的表達(dá)及分布。 數(shù)據(jù)用均數(shù)±標(biāo)準(zhǔn)差(x±s)表示。單因素方差分析進(jìn)行組間比較,有顯著差異者用最小顯著差法進(jìn)行兩兩比較,以p0.05 為有顯著差異。 結(jié)果:各組不同時(shí)間點(diǎn)OPB 和IPB 的COHb 含量和血液及肺、腎組織勻漿的SOD 活性、MDA 含量。①與同時(shí)間點(diǎn)Sham 組相比,CLP 組2h、4h、6hOPB 和IPB 的COHb含量及其差值(OPB-IPB)均顯著升高(P 均0.05),且相鄰時(shí)間點(diǎn)間也有顯著差異(P 均0.05),并呈遞增趨勢(shì),血液及肺、腎組織勻漿的SOD 活性顯著降低(P 均0.05 或0.01),相鄰時(shí)間點(diǎn)間也有顯著差異(P 均0.05 或0.01),呈遞減趨勢(shì),而MDA 含量則顯著升高(P 均0.05 或0.01),呈遞增趨勢(shì);②與同時(shí)間點(diǎn)CLP 組相比,CLP+Hemin 組2h、
[Abstract]:Objective: septic shock caused by abdominal infection is a common clinical pathological process. It even leads to multiple organ dysfunctionsyndrome with multiple organ dysfunction syndrome. MODS. Lung and kidney are often involved organs, mainly for endotoxin induced inflammatory mediators release out of control, thus causing organ damage, but its specific mechanism has not been fully understood. Oxidative stress may be one of the main mechanisms of lung and kidney injury. It has been shown that carbon monoxide can inhibit the production of inflammatory factors. Oxygen free radical injury was inhibited, but cecal ligation andpuncture was ligated and perforated by cecum ligation. Whether lung and kidney injury also have protective effect on septic shock. In this study, CLP was used to establish septic shock model. Heme oxygenase of heme oxygenase was used. ) and zinc protoporphyrin zinc protoporphyrin. To investigate the protective effect of endogenous CO on lung and kidney injury and its possible mechanism. Methods: male Sprague Dawley SD rats, weighing 200,250g, were randomly divided into four groups. Sham-operation group (n = 24): intraperitoneal injection of 25% uratan (4 mg / kg) was performed through the median abdominal incision, without ligation at the root of the cecum, and then sutured layer by layer. In the CLP group, the caecum root was ligated after laparotomy, and two holes (1 cm apart, sutured) were punctured on the cecum serosa surface opposite to the mesentery with a needle of 18 (1 cm apart). Hemin group: operation In the first 10 minutes, 10 mg 路kg ~ (-1) 路kg ~ (-1) of Heminine was injected into the sublingual vein. The rest of the patients were treated with CLP. ZnPP group: 10 minutes before operation, 10 mg / kg of ZnPP was injected into the sublingual vein, and the other operation was the same as that in the CLP group. Each group was treated with CLP for 4 hours after the establishment of the model. The left jugular vein was intubated to the root of the aorta at 6 h from the right jugular vein to the right atrium. The blood collected from the left jugular vein represented the lung blood Out-going pulmonaryblood. In order to detect carboxyhemoglobin (carboxyhemoglobin), OPBand pulmonary blood cells were used to detect carboxyhemoglobin. The level of COHb, which represents the content of CO, continues to be exorcised from the jugular vein to kill the animals, to collect the lung and kidney tissue, to centrifuge the blood sample and to take the supernatant and the lung. The homogenate of kidney tissue was prepared to detect the activity of superoxide dismutase (SOD) in blood, lung and kidney. The content of malondialdehyde (MDA) and the pathological changes of lung and kidney were observed under light microscope. The expression and distribution of HO-1 were observed by immunohistochemical staining. The data were expressed as mean 鹵standard deviation (x 鹵s). Single factor ANOVA was used to compare the two groups, and the least significant difference was used to compare the two groups, with p0.05 as the significant difference. Results: the COHb content of OPB and IPB and the activity of SOD in kidney homogenate were compared with those in Sham group at different time points. The COHb content and the difference of OPB and IPB in CLP group were significantly higher than those in control group (P < 0.05). There were also significant differences between adjacent time points (P 0.05 or 0.01). The activity of SOD in blood, lung and kidney homogenate decreased significantly (P 0.05 or 0.01). There were also significant differences between adjacent time points (P 0.05 or 0.01), but the content of MDA increased significantly (P 0.05 or 0.01). 2Compared with the CLP group at the same time point for 2 h,
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2005
【分類號(hào)】：R363

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 王新穎,李寧;內(nèi)毒素激活細(xì)胞信號(hào)傳導(dǎo)機(jī)制的研究進(jìn)展[J];腸外與腸內(nèi)營(yíng)養(yǎng);2001年03期

，

本文編號(hào)：1481494