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大鼠缺血性結(jié)腸炎模型的建立及用PGE1、SF治療效果的研究

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【摘要】:目的:一、建立大鼠缺血性結(jié)腸炎模型并探討其發(fā)病機制。 二、使用不同劑量的脂微球前列腺素E1(Lipo-PGE1)對缺血性結(jié)腸炎大鼠進(jìn)行治療,評價其治療效果及探討治療機制,為臨床用藥提供理論依據(jù)。 三、使用不同劑量的阿魏酸鈉(SF)對缺血性結(jié)腸炎大鼠進(jìn)行治療,評價SF治療效果及探討治療機制,為治療缺血性結(jié)腸炎提供新的途徑。 方法:一、光化學(xué)法制備大鼠缺血性結(jié)腸炎模型:靜脈注射光敏劑PSD-007后,用激光照射近端結(jié)腸。分別在照射后0、1、3、5、7、14天等不同時間點處死大鼠。檢測結(jié)腸粘膜組織的LI、SOD、MDA和血清TNF-α的動態(tài)變化。 二、用不同劑量Lipo-PGEl治療缺血性結(jié)腸炎大鼠:對照組(生理鹽水)、小劑量組(0.5ug/kg)、中劑量組(1ug/kg)、大劑量組(2ug/kg)。各組均連續(xù)用藥五天后全部處死,檢測LI、SOD、MDA和6-keto-PGFl_α、TXB2及6-keto-PGFl_α/TXB2的變化,分析TNF-α、ICAM-1在結(jié)腸組織的表達(dá)情況。 三、用不同劑量的SF來治療缺血性結(jié)腸炎大鼠,分為:對照組(生理鹽水)、小劑量組(20mg/kg),中劑量組(40mg/kg)、大劑量組(80mg/kg),各組均連續(xù)用藥五天后全部處死,檢測LI、ET-1、SOD、MDA和6-keto-PGFl_α、TXB2及6-keto-PGFl_α/TXB2的變化,分析TNF-α、ICAM-1在結(jié)腸組織的表達(dá)情況。 結(jié)果:一、模型組大鼠經(jīng)激光照射后出現(xiàn)進(jìn)食水減少、活動度減弱、排便增多及暗紅色血便等表現(xiàn),LI隨時間增加而加重,第5天達(dá)到最高點(3.25±0.46,P0.01),之后逐步下降,到第14天基本恢復(fù)正常;SOD活性隨時間而下降,第3天到達(dá)最低點(19.12±6.70,P0.01),MDA含量隨時間而增加,第3天到達(dá)最高點(30.38±4.41,P0.01);TNF-α含量隨時間而增加,第5天到達(dá)最高點(1.89±0.38,P0.01)。上述指標(biāo)均在第14天恢復(fù)正常。SOD與LI呈負(fù)相關(guān),相關(guān)系數(shù)-0.7223(P0.01);MDA、TNF-α與LI呈正相關(guān),
[Abstract]:Objective: 1. To establish a rat model of ischemic colitis and to explore its pathogenesis. Second, different doses of lipid microsphere prostaglandin E1 (Lipo-PGE1) were used to treat ischemic colitis rats, to evaluate the therapeutic effect and explore the therapeutic mechanism, to provide a theoretical basis for clinical use of drugs. Third, different doses of sodium ferulate (SF) were used to treat ischemic colitis rats, to evaluate the therapeutic effect of SF and explore the therapeutic mechanism, so as to provide a new way for the treatment of ischemic colitis. Methods: 1. The model of ischemic colitis in rats was made by photochemical method. After intravenous injection of photosensitizer PSD-007, the proximal colon was irradiated by laser. Rats were killed at 0, 1, 3, 5, 7, 14 days after irradiation. The dynamic changes of LI,SOD,MDA and serum TNF- 偽 in colonic mucosa were detected. Two, rats with ischemic colitis were treated with different doses of Lipo-PGEl: control group (saline), low dose group (0.5ug/kg), middle dose group (1ug/kg), high dose group (2ug/kg). All the rats in each group were killed for 5 days. The changes of LI,SOD,MDA, 6-keto-PGFL _ 偽, TXB2 and 6-keto-PGFL _ 偽 / TXB2 were detected, and the expression of TNF- 偽 and ICAM-1 in colon tissue were analyzed. The rats with ischemic colitis were divided into three groups: control group (saline), low dose group (20mg/kg), middle dose group (40mg/kg) and high dose group (80mg/kg). All the rats in each group were killed for 5 days. The changes of LI,ET-1,SOD,MDA, 6-keto-PGFL _ 偽, TXB2 and 6-keto-PGFL _ 偽 / TXB2 were detected, and the expression of TNF- 偽 and ICAM-1 in colon tissue were analyzed. Results: 1. After laser irradiation, the rats in the model group showed decreased intake of water, decreased activity, increased defecation and dark red blood stool. LI increased with the increase of time and reached the highest point on the 5th day (3.25 鹵0.46, P0.01). After that, it gradually decreased and returned to normal on the 14th day. The activity of SOD decreased with time and reached the lowest point on the third day (19.12 鹵6.70, P0.01). The content of), MDA increased with time and reached the highest point on the third day (30.38 鹵4.41, P0.01). The content of TNF- 偽 increased with time and reached the highest point on the 5th day (1.89 鹵0.38, P0.01). Sod was negatively correlated with LI, the correlation coefficient was-0.7223 (P0.01), and MDA,TNF- 偽 was positively correlated with LI.
【學(xué)位授予單位】:中國人民解放軍軍醫(yī)進(jìn)修學(xué)院
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2006
【分類號】:R574.62;R-332

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