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学科主题: 内科学
题名:
二氧化硫对脓毒症大鼠致急性肺损伤炎性介质的调节作用
作者: 吕雪雅
答辩日期: 2016-05-18
导师: 赵斌
专业: 内科学
授予单位: 北京大学
授予地点: 北京大学第四临床医学院
学位: 硕士
关键词: [二氧化硫] ; [脓毒症] ; [肺损伤] ; [炎性介质]
其他题名: Regulative effects of Sulfur dioxide on Inflammatory mediators on acute lung injury in rats
分类号: R563.1
摘要:

目的:急性肺损伤(acute lung injury, ALI)是指机体遭受严重感染、创伤、休克、酸中毒及有害气体吸入等多种因素打击后,出现弥漫性肺泡-毛细血管膜损伤所致的肺水肿和微肺不张等病理改变,临床表现为急性呼吸窘迫和顽固性低氧血症。现已发现效应细胞、炎症介质和氧化应激多种因素共同参与了肺损伤的发病过程。但确切机制仍未阐明。本实验以盲肠结扎穿刺术诱导大鼠ALI模型为研究对象,探索SO2对盲肠结扎穿刺术诱导大鼠肺损伤炎症因子调节作用。方法:雄性Sprague Dawley大鼠40只,随机被分入假手术(sham) 组(n=10)、sham+SO2组(n=10)、盲肠结扎穿刺术(CLP)组(n=10)、CLP+SO2组(n=10)。Sham组在开腹后仅翻动肠道后关腹,不予手术结扎穿刺及皮下注射NS补液;sham+SO2组大鼠在实施开腹手术之前30分钟腹腔注SO2供体(Na2SO3/NaHSO3)0.54mmol/kg;CLP组开腹后实施盲肠结扎穿刺术,术后给与皮下注射NS补液; CLP+ SO2组大鼠在实施盲肠结扎穿孔术前30分钟腹腔注射SO2供体(Na2SO3/NaHSO3) 0.5ml/kg。以上4组观察大鼠一般情况12h后处死动物,对大鼠肺组织大体以及显微镜下形态学观察,测量肺湿干重量比(wet/dry weight,W/D),肺损伤的组织学半定量评分(index of quantitative assessment,IQA);检测血浆SO2浓度;ELISA法检测血浆白细胞介素6、8(interleukins-6,IL6、interleukins-8,IL8)及单核细胞趋化蛋白-1(Monocyte chemotactic protein-1,MCP-1)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)含量。结果: (1)各组肺损伤程度比较:与sham组相比,CLP组大鼠肺间质和肺泡腔IQA增高(P<0.05),W/D比增高(P<0.05)。与CLP组相比,CLP+SO2组大鼠肺损伤程度减轻,IQA降低(P<0.05),W/D比降低(P<0.05)。(2)各组大鼠血浆SO2含量比较:与sham组相比,CLP组大鼠血浆SO2含量显著减低(P<0.05)。与CLP组相比,CLP+SO2组大鼠血浆SO2含量显著升高(P<0.05)。(3) ①各组大鼠血浆IL-6水平:与sham组相比,CLP组血浆IL-6增高(P<0.01)。与CLP组相比,CLP+SO2组大鼠血浆IL-6降低(P<0.05)。②各组大鼠血浆IL-8水平:与sham组相比,CLP组血浆IL-8增高(P<0.01)。与CLP组相比,CLP+SO2组大鼠血浆IL-8降低(P<0.05)。③各组大鼠血浆MCP-1水平:与sham组相比,CLP组血浆MCP-1增高(P<0.01)。与CLP组相比,CLP+SO2组大鼠血浆MCP-1降低(P<0.01)。④各组大鼠血浆MCP-1水平:与sham组相比,CLP组血浆TNF-α增高(P<0.01)。与CLP组相比,CLP+SO2组大鼠血浆TNF-α降低(P<0.05)结论:盲肠结扎穿刺术可诱导大鼠产生脓毒血症肺损伤,而内源性SO2可以通过抑制IL-6、IL-8、IMCP-1、TNF-α进而减轻炎症因子的表达起到保护作用。

英文摘要:

Objective: Acute lung injury (ALI) is often a consequence of acute diffuse damage include alveolar epithelium cells、pulmonary capillary endothelial cells and lung interestitials. The main pathogenesis is diffuse alveolar damage (DAD).It is acterized by acute progressing respiratory distress, refractory hypoxemia and noncardiac lung edema in early stage and severe respiratory failure in developed stage, which is named acute respiratory distress syndrome(ARDS).Many effector cells and inflammatory mediators are involved in the process of the injury. The pathogenesis of ALI is complex and has not been well clarified yet. In this experiment, cecal ligation and puncture-induced ALI rat model for the study, to explore the SO2 to cecal ligation and puncture-induced lung injury in rats with inflammatory cytokines regulation. Method: Forty male Sprague Dawley rats were randomly divided into sham-operated (sham) group (n = 10), sham + group (n = 10), cecal ligation and puncture (CLP) group (n = 10), CLP + SO2group (n = 10). Sham group, the abdomen was closed after just flip open the intestinal tract, not surgical ligation and puncture and NS subcutaneous rehydration; Rats in sham+SO2group were first injected with Na2SO3/NaHSO3 (0.54mmol/kg,intraperitoneal) before Sham operation;CLP group were given , cecal ligation and puncture;Administration of the erivatives, sodium sulfite/sodium bisulfite (Na2SO3/NaHSO3) at 0.54mmol/kg, by intraperitoneal injection for 30 min before CLP treatment was applied in CLP+SO2group.All the rats were scarificed afer 12h after the surgery.Index of quantitative assessment of histological lung injury (IQA), wet/dry weight ratio (W/D) and the level of SO2 in plasma were measured. IL6, IL8, IL10, MCP-1 and TNF-α were measured by ELISA. Result: (1)Comparison of lung injury rats groups:Compared with sham rats, CLP rats experienced significantly lung injury,increased IQA(P<0.05),increased lung W/D ratio(P<0.05).Compared with CLP rats,administration of SO2 in CLP rats significantly decreased lung injury,decreased IQA(P<0.05) ,decreased lung W/D ratio(P<0.05).(2) Comparison of SO2 content of plasma rats groups : Compared with sham rats,SO2 content of CLP rats significantly reduced(P<0.05).Compared with CLP rats,SO2 content of administration of SO2 in CLP rats significantly increased(P<0.05).(3) ①Comparison of IL-6 level of plasma rats groups: Compared with sham rats, IL-6 level of CLP rats significantly increased (P<0.01).Compared with CLP rats, administration of SO2 in CLP rats significantly decreased IL-6 level of plasma (P<0.05) .②Comparison of IL-8 level of plasma rats groups: Compared with sham rats, IL-8 level of CLP rats significantly increased (P<0.01).Compared with CLP rats, administration of SO2 in CLP rats significantly decreased IL-8 level of plasma (P<0.05) .③Comparison of MCP-1 level of plasma rats groups: Compared with sham rats, MCP-1 level of CLP rats significantly increased (P<0.01).Compared with CLP rats, administration of SO2 in CLP rats significantly decreased MCP-1 level of plasma (P<0.05) .④Comparison of TNF-α level of plasma rats groups: Compared with sham rats, TNF-αlevel of CLP rats significantly increased (P<0.01).Compared with CLP rats, administration of S in CLP rats significantly decreased TNF-αlevel of plasma (P<0.05) . Conclusion: Cecal ligation and puncture can induce acute lung injury, while the endogenous SO2 can inhibit IL-6、IL-8、IMCP-1, TNF-α thereby reducing the expression of inflammatory factors by playing a protective role.

语种: 中文
相关网址: 查看原文
内容类型: 学位论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/124763
Appears in Collections:北京大学第四临床医学院_学位论文

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作者单位: 北京大学第四临床医学院

Recommended Citation:
吕雪雅. 二氧化硫对脓毒症大鼠致急性肺损伤炎性介质的调节作用[D]. 北京大学第四临床医学院. 北京大学. 2016.
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