高压氧对油酸诱导大鼠急性肺损伤作用的实验研究

目的 探讨高压氧(HBO)对油酸(OA)诱导大鼠急性肺损伤(ALI)的干预作用.方法 80只SD大鼠按随机数字表法分为4组.OA组30只,经鼠尾静脉注射OA 0.15 ml/kg制备ALI模型,分别于制模后4 h、3 d、7 d各随机活杀10只;OA+HBO组20只,在HBO治疗箱给予2.5 atm(1 atm=101.325 kPa)下单次治疗90 min,分别于HBO治疗后3 d、7 d各随机活杀10只;单纯HBO干预组20只,分别于HBO治疗后3 d、7 d各随机活杀10只;另设正常对照组10只.取腹主动脉血进行血气分析,测定血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、IL-6;取左肺标本,观察大体形态改变及镜下病理学改变;取右肺,测定湿/干重(W/D)比值.结果 OA组4 h后动脉血氧分压(PaO2,mm Hg,1 mm Hg=0.133 kPa)由107.70±5.37降至57.40±2.63;肉眼可见肺脏明显淤血、水肿;光镜下肺泡正常结构消失,间质水肿增宽,大量炎性细胞浸润,毛细血管明显扩张、透明膜形成;W/D比值较正常对照组明显增加(6.94±0.44比4.59±0.44,P<0.05),血清TNF-α、IL-1β、IL-6水平升高[TNF-α(μg/L):18.52±1.20比5.27±0.61,IL-1β(μg/L):13.73±1.37比6.13±1.51,IL-6(μg/L):14.51±1.21比11.14±0.89].经HBO治疗3 d、7 d时PaO2(mm Hg,3 d:79.20±1.68比59.00±2.70,7 d:94.30±3.77比74.00±3.85)、肺W/D比值(3 d:7.43±0.73比9.82±0.99,7 d:6.75±1.14比8.77±1.60)均较OA组同期有不同程度改善(P<0.05或P<0.01).治疗3 d后HBO有降低血清中IL-1β(μg/L)的作用(6.46±1.99比9.09±1.09,P<0.05).结论 HBO治疗有改善ALI大鼠氧合,促进肺水吸收、抑制部分炎症介质产生的作用.     

Heparanase pretreatment attenuates endotoxin-induced acute lung injury in rats

A central event of systemic inflammation and septic organ injury is infiltration of tissues with polymorphonuclear neutrophils, likely modulated by the integrity of the extracellular matrix underlying the vascular endothelium. In the present study, the effect of matrix-modifying endoglycosidase (heparanase) on endotoxin (LPS)-induced inflammatory lung injury was investigated in rats. Animals were treated with heparanase or LPS or pretreated with heparanase before LPS injection, and acute lung injury was verified histologically and characterized by analysis of bronchoalveolar lavage fluids. Pretreatment with heparanase attenuated the mortality of animals and preserved the histological structure of the lungs. Furthermore, polymorphonuclear neutrophil accumulation and activation, analyzed by myeloperoxidase release and reactive oxygen species production associated with lung injury, were significantly reduced upon heparanase pretreatment. In addition, heparanase pretreatment elevated the IL-10 levels in the pulmonary compartment. Moreover, results from in vitro experiments have identified monocyte-derived IL-10 as an important mediator used by heparanase to suppress inflammatory reactions. The protective effect of heparanase may indicate a novel therapeutic strategy for sepsis.     

高压氧对重型颅脑损伤大鼠血浆内皮素含量的影响

目的:研究高压氧对重型颅脑损伤小鼠血浆内皮素的变化的影响。方法:将100只健康Wistar大鼠按随机数字表法分为创伤对照组和1次/d高压氧疗组,利用自由落体原理制成重型颅脑损伤模型,观测伤后1次/d高压氧治疗后8,24,48,72,96h血浆内皮素含量变化。结果:高压氧治疗组血浆内皮素含量:大鼠伤后8,24,48,72,96h为(199.84±20.34),(200.38±21.17),(203.12±19.11),(206.81±21.54),(211.24±23.57)ng/L较同期对照组犤(231.32±17.18),(234.03±18.24),(240.39±16.37),(254.32±17.25),(268.91±36.65)ng/L犦显著降低(t=3.72～5.46,P<0.01)。结论:重型颅脑损伤后血浆内皮素活性升高,高压氧治疗通过纠正脑缺氧,在一定程度上抑制了内皮细胞产生、释放内皮素,从而减轻了脑水肿和血管痉挛避免了脑继发性损害。     

高压氧对大鼠颅脑创伤后脑水肿和脂质过氧化物丙二醛的影响

背景脑创伤后脑组织水肿与缺氧再灌注后氧自由基的产生有关.高压氧能减轻脑水肿,改善组织缺氧.目的观察大鼠颅脑创伤后高压氧对脑水肿和脂质过氧化物的影响.设计随机对照实验.单位第三军医大学大坪医院野战外科研究所.材料实验于2004-03/06在第三军医大学大坪医院野战外科研究所高压氧科、四室完成.选取3个月龄Wistar大鼠58只,体质量(256±23)g,清洁级.方法将58只大鼠随机分为对照组17只,脑创伤组22只和高压氧组19只.对照组不进行撞击试验.脑创伤组和高压氧组麻醉后均采用BIM-Ⅲ型撞击机撞击大鼠右侧颅顶,复制闭合性颅脑损伤.高压氧组致伤后置于2个绝对大气压的高压氧舱2 h,大鼠于伤后24 h心脏取血处死.主要观察指标观察大鼠颅脑创伤后脑组织含水率、伊文斯蓝含量及脑组织、血浆脂质过氧化物丙二醛含量.结果实验致伤动物41只,伤后24 h死亡7只.其中高压氧组2只,脑创伤组5只.进入结果分析34只.①脑组织含水率右脑脑创伤组.明显高于高压氧组和对照组[(79.06±0.52,78.38±0.37,78.21±0.25)%,t=3.022～3.285,＜0.01].脑创伤组右脑明显高于左脑[(79.06±0.52,78.57±0.14)%,t=2.651,P＜0.05].②脑组织丙二醛含量右脑脑创伤组明显高于高压氧组和对照组[(197.28±31.49,167.65±25.88,145.07±30.45)nmol/g,t=2.231～3.347,＜0.01～0.05].脑创伤组右脑明显高于左脑[(197.28±31.49,161.01±22.05)nmol/g,t=2.443,P＜0.05].③血浆中丙二醛含量脑创伤组明显高于对照组[(2.69±0.54,1.94±0.40)μmol/L,t=2.473,P＜0.05].结论脑创伤后行高压氧治疗,大鼠伤侧脑组织含水率、丙二醛及血浆丙二醛含量明显低于非治疗组,提示高压氧对颅脑创伤有治疗作用.     

高压氧对大鼠颅脑创伤后脑水肿和脂质过氧化物丙二醛的影响

背景：脑创伤后脑组织水肿与缺氧再灌注后氧自由基的产生有关.高压氧能减轻脑水肿,改善组织缺氧.目的：观察大鼠颅脑创伤后高压氧对脑水肿和脂质过氧化物的影响.设计：随机对照实验.单位：第三军医大学大坪医院野战外科研究所.材料：实验于2004-03/06在第三军医大学大坪医院野战外科研究所高压氧科、四室完成.选取3个月龄Wistar大鼠58只,体质量（256&;#177;23）g,清洁级.方法：将58只大鼠随机分为对照组17只,脑创伤组22只和高压氧组19只.对照组不进行撞击试验.脑创伤组和高压氧组麻醉后均采用BIM-Ⅲ型撞击机撞击大鼠右侧颅顶,复制闭合性颅脑损伤.高压氧组致伤后置于2个绝对大气压的高压氧舱2 h,大鼠于伤后24 h心脏取血处死.主要观察指标：观察大鼠颅脑创伤后脑组织含水率、伊文斯蓝含量及脑组织、血浆脂质过氧化物丙二醛含量.结果：实验致伤动物41只,伤后24 h死亡7只.其中高压氧组2只,脑创伤组5只.进入结果分析34只.①脑组织含水率：右脑脑创伤组.明显高于高压氧组和对照组[（79.06&;#177;0.52,78.38&;#177;0.37,78.21&;#177;0.25）%,t=3.022～3.285,＜0.01].脑创伤组右脑明显高于左脑[（79.06&;#177;0.52,78.57&;#177;0.14）%,t=2.651,P＜0.05].②脑组织丙二醛含量：右脑脑创伤组明显高于高压氧组和对照组[（197.28&;#177;31.49,167.65&;#177;25.88,145.07&;#177;30.45）nmol/g,t=2.231～3.347,＜0.01～0.05].脑创伤组右脑明显高于左脑[（197.28&;#177;31.49,161.01&;#177;22.05）nmol/g,t=2.443,P＜0.05].③血浆中丙二醛含量：脑创伤组明显高于对照组[（2.69&;#177;0.54,1.94&;#177;0.40）μmol/L,t=2.473,P＜0.05].结论：脑创伤后行高压氧治疗,大鼠伤侧脑组织含水率、丙二醛及血浆丙二醛含量明显低于非治疗组,提示高压氧对颅脑创伤有治疗作用.     

Hypothermia protects against endotoxin-induced acute lung injury in rats

OBJECTIVE: Hypothermia in humans and animals is known to decrease the number and function of circulating neutrophils. Because an activation of circulating neutrophils and their sequestration into the lung are important pathogenetic phenomena in endotoxin-associated lung injury, we conjectured that hypothermia could prevent this type of lung injury. DESIGN AND SETTING: Animal study at a university-affiliated research institute. SUBJECTS: Thirty-six Sprague-Dawley rats. INTERVENTIONS: After anesthesia, the rats were randomly assigned to normothermia (37 degrees C, rectal temperature) or hypothermia (27 degrees C), which was induced by surface cooling. After 1 h of stable temperature, the rats were administered intratracheal doses of lipopolysaccharide (LPS; 3 mg/kg) (normothermia-LPS; hypothermia-LPS) or an equivalent volume of normal saline (normothermia-saline; hypothermia-saline). The rectal temperature was maintained within +/-1 degrees C of the target temperature for 6 h after the intratracheal treatment. MEASUREMENTS AND RESULTS: Compared with the normothermia-LPS group, the neutrophil count in bronchoalveolar lavage (BAL) fluid (p=0.002) and the myeloperoxidase activity of lung tissues (p=0.002) of the hypothermia-LPS group were both lower. Compared with the normothermia-LPS group, the BAL interleukin-1beta level of the hypothermia-LPS group was lower (p<0.001), whereas the BAL interleukin-10 level of the hypothermia-LPS group was higher (p=0.026). Compared with the normothermia-LPS group, the histologic scores for acute lung injury of the hypothermia-LPS group were lower (p=0.007). CONCLUSIONS: Hypothermia pretreatment decreased the pulmonary sequestration of neutrophils, induced a favorable balance between pro- and anti-inflammatory cytokines, and attenuated histologic injury in endotoxin-challenged rats.     

Insulin attenuates endotoxin-induced acute lung injury in conscious rats

OBJECTIVES: To investigate the effects of insulin on the acute lung injury induced by lipopolysaccharide using a conscious rat model. DESIGN: Prospective, randomized, controlled animal study. SETTING: University research laboratory. SUBJECTS: A total of 190 adult male Sprague-Dawley rats weighing 250-300 g. INTERVENTIONS: Endotoxemia was induced by intravenous infusion of lipopolysaccharide. Lipopolysaccharide at various doses (0, 1, 5, 10, 20, and 30 mg/kg, n=10 for each dose) was administered intravenously in 20 mins. Insulin infusion at doses of 0.5, 1, and 5 microU/kg/min was given 5 mins before lipopolysaccharide administration. Plasma glucose was clamped at 90-110 mg/dL by infusion of 10-80% glucose solution. Insulin and glucose infusion (0.01 mL/min) was started 5 mins before lipopolysaccharide and continued for 120 mins. The rats received a total of 60, 120, and 600 microU/kg insulin as well as 0.12, 0.36, and 0.96 g of glucose in respective groups. The animals were then observed for 4 hrs. MEASUREMENTS AND MAIN RESULTS: The extent of acute lung injury was evaluated by lung weight/body weight ratio, lung weight gain, protein concentration in bronchoalveolar lavage, and exhaled nitric oxide. We also measured plasma nitrate/nitrite and methyl guanidine. In addition, histopathologic changes of the lung were examined. Lipopolysaccharide caused systemic hypotension and severe acute lung injury with increases in plasma nitrate/nitrite and methyl guanidine. Pretreatment with insulin infusion at doses of 0.5, 1, and 5 microU/kg/min mitigated or prevented systemic hypotension and the development of acute lung injury, depending on the dose. Insulin also attenuated the lipopolysaccharide-induced increases in nitrate/nitrite and methyl guanidine. CONCLUSIONS: Insulin is effective in reducing or preventing the lipopolysaccharide-induced increases in plasma nitrate/nitrite and methyl guanidine and the occurrence of acute lung injury.     

高压氧干预对大鼠肾缺血再灌注损伤保护作用的实验研究

目的探讨高压氧(HBO)对大鼠肾缺血再灌注损伤(IRI)的作用及其机制。 方法建立大鼠肾IRI模型,54只Wistar大鼠分为假手术组、肾IRI组和HBO治疗组,每组18只。各组分别于再灌注后1,3,5 h（每个时间点6只）采血测定血浆肿瘤坏死因子（TNF-α）、丙二醛（MDA）的水平及肾功能［肌酐(SCr）、尿素氮（BUN)］;同时肾组织HE染色后光镜观察病理变化。 结果(1)肾IRI组血浆TNF-α、MDA和SCr、BUN的水平明显高于假手术组(P<0.05);与肾IRI组相比,HBO治疗组血浆TNF-α、MDA和SCr、BUN的水平显著降低(P<0.05)。(2)假手术组各时间点肾小球、肾小管上皮细胞结构正常;肾IRI组随时间延长,肾小球毛细血管、肾小管上皮细胞损伤逐渐加重;HBO治疗后肾损伤的程度明显减轻,再灌注后1 h和3 h肾损伤减轻的程度明显优于再灌注后5 h。 结论TNF-α和MDA促进了肾IRI的发生发展。HBO通过减少TNF-α的生成和防止组织脂质过氧化,明显减轻了肾IRI,保护了肾功能。HBO早期干预更有利于防治肾IRI。     

高压氧对大鼠急性胰腺炎影响的研究

目的 探讨高压氧对大鼠急性胰腺炎的影响.方法 56只SD大鼠随机分组,其中48只分为对照组和高压氧干预组,每组24只,均采用胰管结扎的方法制备胰腺炎模型,造模后每组再随机分为3亚组:每亚组分别在造模后1、3、7 d处死,仅对高压氧治疗组进行高压氧干预.两组均留取胰腺标本及血液使用病理评分评价胰腺标本出血、坏死和水肿方面的差异,并同时使用ELISA法检测血液IL-2、IL-6、IL-10及TNF-α水平.剩余8只为假手术组仅进行开关腹用于验证胰腺炎造模是否成功.结果 造模后第一天胰腺淀粉酶水平在假手术组为(798.50±113.5)U/L,对照组为(3156.2±639.9)U/L,高压氧治疗组为(2973.1±1042.6)U/L,其中假手术组与对照组及高压氧组之间有统计学差异,但对照组及高压氧治疗组之间差异无统计学意义.经过7 d的高压氧治疗之后,胰腺炎大鼠的细胞因子IL-2、IL-6、IL-10及TNF-α浓度水平较对照组明显下降,差异有统计学意义,而在病理评价方面,对胰腺炎的水肿、白细胞浸润、坏死和出血等方面均有改善作用,但仅在出血和坏死方面差异有统计学意义.结论 高压氧治疗组可以显著减少大鼠胰腺腺泡的坏死和出血,但是对于水肿和白细胞浸润方面则并未得到预期的结果.同时高压氧治疗可以显著抑制血液炎症因子的活性.     

季德胜蛇药片对大鼠急性肺损伤的保护作用

目的研究季德胜蛇药片对细菌脂多糖(Lipopolysaccharide,LPS)诱导大鼠急性肺损伤的保护作用。方法50只雄性SD大鼠随机分为6组:正常对照组、地塞米松阳性对照组、LPS模型组及低、中、高三种不同剂量蛇药组。分别用地塞米松和三种不同剂量的蛇药在LPS诱导ALI模型之前预处理大鼠。检测大鼠的肺系数,光镜观察肺组织损伤程度,酶谱法测肺组织匀浆液和支气管肺泡灌洗液上清中MMP2、MMP9酶活力及免疫组织化学方法检测肺组织MMP2、MMP9蛋白表达情况。结果与模型组比较,阳性对照组及蛇药组肺系数均降低(P<0.05),且高剂量组明显低于阳性对照组(P<0.01)。蛇药组肺组织损伤程度、MMP9酶活力均随剂量的增加而减轻或降低,MMP2酶活力亦有不同程度的下降;高剂量组MMP2、MMP9蛋白表达减弱;结论季德胜蛇药片对LPS诱导大鼠急性肺损伤有一定保护作用,其作用机制可能与抑制MMP2、MMP9表达及活性有关。     

血必净注射液对急性肺损伤大鼠氧自由基变化的影响

目的:探讨血必净注射液对急性肺损伤大鼠氧自由基变化的影响.方法:SD大鼠72只随机分为正常对照组、内毒素组(LPS组)和内毒素联合血必净组(LPS+XBJ组),后两组又分别分为给药后1、2、4、12 h 4个亚组,每个亚组8只.采用静脉注射LPS(5 mg/kg)建立急性肺损伤模型.LPS+XBJ组予静脉注射LPS后同时腹腔注射血必净(10 mL/kg),LPS组腹腔注射等量生理盐水(10 mL/kg),正常对照组给予等量生理盐水.观察各组肺组织病理学变化,检测各组肺湿干质量比(W/D)、血清丙二醛(MDA)浓度、超氧化物歧化酶(SOD)活力等的变化.结果:血必净注射液干预可显著降低急性肺损伤大鼠升高的W/D(P<0.05)和血清肺MDA浓度(P<0.01或P<0.05).显著升高急性肺损伤大鼠降低的SOD浓度(P<0.01或P<0.05),减轻肺组织形态学损伤.结论:血必净注射液可抑制氧自由基产生.对LPS所致急性肺损伤大鼠具有肺保护作用.     

Effects of hyperbaric oxygen on intestinal mucosa apoptosis caused by ischemia-reperfusion injury in rats

BACKGROUND:

Hyperbaric oxygen (HBO) is an effective adjuvant therapy for ischemia- reperfusion (I/R) injury of the brain, small intestine and testis in addition to crushing injury. Studies have shown that HBO increases the activity of villi of the ileum 30 minutes after I/R injury. The present study aimed to observe the effect of HBO on apoptosis of epithelial cells in the small intestine during different periods of I/R and to elucidate the potential mechanisms.

METHODS:

Rats were subjected to 60-minute ischemia by clamping the superior mesenteric artery and 60-minute reperfusion by removal of clamping. The rats were randomly divided into four groups: I/R group, HBO precondition or HBO treatment before ischemia (HBO-P), HBO treatment during ischemia period (HBO-I), and HBO treatment during reperfusion (HBO-R). After 60-minute reperfusion, samples of the small intestine were prepared to measure the level of ATP by using the colorimetric method and immunochemical expression of caspase-3. The levels of TNF-α in intestinal tissue were measured using the enzyme-linked immunosorbent assay method (Elisa).

RESULTS:

TNF-α levels were significantly lower in the HBO-I group than in the HBO-P (P<0.05), HBO-R and I/R groups; there was no significant difference between the HBO-R and I/R groups (P>0.05). The expression of caspas-3 was significantly lower in the HBO-I group than in the HBO-P group (P<0.05); it was also significantly lower in the HBO-P group than in the I/R and HBO-R groups (P<0.05). ATP level was significantly lower in the HBO-I group than in the HBO-P group (P<0.05), and also it was significantly lower in the HBO-P group than in the I/R and HBO-R groups (P<0.05).

CONCLUSIONS:

There is an association between HBO, small intestinal I/R injury, and mucosa apoptosis. HBO maintains ATP and aerobic metabolism, inhibites TNF-α production, and thus prevents intestinal mucosa from apoptosis. Best results can be obtained when HBO is administered to patients in the period of ischemia, and no side effects are produced when HBO is given during the period of reperfusion.KEY WORDS: Hyperbaric oxygen, Ischemia-reperfusion injury, Apoptosis     

高压氧治疗对创伤性脑损伤大鼠认知功能的影响

目的:观察高压氧治疗对脑损伤大鼠认知功能的影响及海马区CCL2及其受体CCR2的表达变化。方法:75只成年雄性SD大鼠按数字表法随机分为假手术组(Sham组)、脑外伤组(TBI组)和高压氧治疗组(HBOT组),每组各25只。HBOT组和TBI组均采用Feeney自由落体法制作脑外伤模型,HBOT组每天进行HBO治疗;Sham组暴露硬脑膜不予打击。运用Morris水迷宫测试认知功能;荧光免疫双标检测海马CA1区CCL2和CCR2的表达。实时定量PCR测定损伤侧海马CCL2和CCR2mRNA的表达情况。结果:Morris水迷宫测试结果显示,HBOT组高压氧治疗后7d、14d和21d平均潜伏期下降,同时穿越平台次数增多,与TBI组相比,差异均有显著性意义(P0.05);免疫荧光双染法检测显示,大鼠TBI后海马CA1区CCL2主要表达在星形胶质细胞,CCR2主要表达在神经元;实时定量PCR显示,脑损伤后3—21d损伤侧海马CCL2 mRNA、CCR2 mRNA水平明显上升,差异有显著性意义;高压氧治疗后海马CCL2 mRNA明显下降,与TBI组相比,7d组、14d组及21d组差异有显著性意义(P0.05)。高压氧治疗7d、14d后海马CCR2 mRNA明显下降,与TBI组相比,7d组及14d组差异有显著性意义(P0.05)。结论:HBO治疗可以改善创伤性脑损伤大鼠认知功能,其机制可能与海马CCL2/CCR2表达下调有关。     

高压氧对疲劳大鼠肝损伤的保护作用

目的:探讨高压氧暴露对疲劳大鼠肝脏损伤的保护作用及机制.方法:4周龄健康雄性(Sprague Dawley,SD)大鼠30只,随机分为3组:对照组、疲劳模型组、疲劳高压氧暴露组,每组10只.建立大鼠游泳致力竭疲劳模型并通过高压氧暴露进行恢复;8周实验后取每只大鼠两块肝脏组织,其中一块取每只大鼠的肝脏相同部位,光镜观察肝脏组织的病理变化;另一块取肝右叶5g,制备成10％的肝组织匀浆,检测匀浆液的丙二醛(MDA)、超氧化物歧化酶(SOD)含量的变化.结果:①疲劳高压氧暴露组大鼠游泳时间明显长于疲劳模型组(P＜ 0.05).②对照组、疲劳模型组和疲劳高压氧暴露组大鼠肝脏组织MDA含量存在显著性差异(P＜0.01),进一步两两比较显示,疲劳模型组MDA含量显著高于其他两组(P＜0.01);并且三组肝脏组织SOD活性存在显著性差异(P＜0.01),进一步两两比较发现,疲劳模型组SOD活性显著低于其他两组(P＜0.01).③对照组肝组织结构正常,疲劳模型组肝索断裂明显,肝窦变窄,中央静脉结构紊乱,肝小叶内轮廓不清,肝细胞肿胀,核变大,胞浆空淡明显可见,部分肝小叶中出现散在的点灶状坏死肝细胞,经高压氧治疗后,疲劳高压氧暴露组中央静脉仍然扩张并伴有淤血,但结构完整,肝索断裂呈散在分布,较疲劳模型组稍有缓解.结论:高压氧暴露能有效加长大鼠游泳时间,降低疲劳大鼠肝脏MDA含量,提高SOD活性,改善肝脏组织的病理变化,从而对疲劳大鼠肝脏损伤起到保护作用.     

Danaparoid sodium inhibits systemic inflammation and prevents endotoxin-induced acute lung injury in rats

Introduction

Systemic inflammatory mediators, including high mobility group box 1 (HMGB1), play an important role in the development of sepsis. Anticoagulants, such as danaparoid sodium (DA), may be able to inhibit sepsis-induced inflammation, but the mechanism of action is not well understood. We hypothesised that DA would act as an inhibitor of systemic inflammation and prevent endotoxin-induced acute lung injury in a rat model.

Methods

We used male Wistar rats. Animals in the intervention arm received a bolus of 50 U/kg of DA or saline injected into the tail vein after lipopolysaccharide (LPS) administration. We measured cytokine (tumour necrosis factor (TNF)α, interleukin (IL)-6 and IL-10) and HMGB1 levels in serum and lung tissue at regular intervals for 12 h following LPS injection. The mouse macrophage cell line RAW 264.7 was assessed following stimulation with LPS alone or concurrently with DA with identification of HMGB1 and other cytokines in the supernatant.

Results

Survival was significantly higher and lung histopathology significantly improved among the DA (50 U/kg) animals compared to the control rats. The serum and lung HMGB1 levels were lower over time among DA-treated animals. In the in vitro study, administration of DA was associated with decreased production of HMGB1. In the cell signalling studies, DA administration inhibited the phosphorylation of IκB.

Conclusion

DA decreases cytokine and HMGB1 levels during LPS-induced inflammation. As a result, DA ameliorated lung pathology and reduces mortality in endotoxin-induced systemic inflammation in a rat model. This effect may be mediated through the inhibition of cytokines and HMGB1.     

高血压治疗对损伤后生长相关蛋白-43在神经系统表达的影响

目的 探讨应用高压氧治疗大鼠脑缺血再灌注损伤后,生长相关蛋白-43( GAP-43)在神经系统的表达. 方法 成年健康雄性SD大鼠32只,随机分为高压氧组(n=16)和高压空气组(n=16),每组再分为脑缺血再灌注模型组(n=8)和假手术组(n=8).应用线栓法制备大鼠脑缺血再灌注动物模型,免疫组化法检测GAP-43在...     

高压氧治疗对大鼠重度脑创伤后炎性反应的影响

目的观察高压氧治疗对重度脑创伤大鼠其脑组织内炎性细胞因子水平的影响及大鼠脑组织病理学改变,并探讨高压氧治疗的作用机制。方法将SD大鼠随机分为假手术组、高压氧组及脑创伤组。采用高压气体冲击脑组织制作大鼠局部脑创伤模型。分别于术后3h、1d、3d、5d及7d时观察大鼠脑组织病理学改变;同时应用放射免疫检测技术测定脑创伤组及高压氧组在上述各时间点时脑内TNF-α、IL-6、IL-8及IL-10的水平。结果当大鼠发生脑创伤后,上述各炎性细胞因子水平较假手术组均有不同程度提高,经高压氧治疗后,发现炎性细胞向脑组织内浸润现象减缓,并有大量小胶质细胞、星形胶质细胞聚集、增生,而且高压氧组大鼠脑组织内上述炎性细胞因子在各时间点均较脑创伤组降低(均P<0.01);与假手术组比较,差异无统计学意义(P>0.05)。结论高压氧可抑制炎性细胞向脑创伤组织处浸润,降低各炎性细胞因子水平,促进小胶质细胞、星形胶质细胞聚集、增生,具有保护受损脑组织的功效。     

高压氧对大鼠肠缺血-再灌注损伤致细胞凋亡的影响

目的 观察大鼠在小肠缺血-再灌注(I/R)不同时期应用高压氧(HBO)治疗对小肠黏膜细胞凋亡的影响,并探讨其作用机制.方法 采取大鼠肠系膜上动脉(SMA)钳夹缺血60 min,松钳夹再灌注60 min,建立S-D大鼠小肠I/R损伤模型,并随机(随机数字法)分成4组:I/R组、缺血前HBO治疗组或HBO预处理组(HBO-P)、缺血期HBO治疗组(HBO-I)和再灌注期HBO治疗组(HBO-R).再灌注60 min后,取回肠末端小肠标本.采用酶连免疫吸附试验法(Elisa)检测肠道组织TNF-α,用比色法检测肠道组织匀浆含量ATP,用免疫组化法检测小肠组织中半胱氨酸天门冬氨酸特异蛋白酶(Caspase-3)的表达.数据以均数±标准差(-x±s)表示,采用单因素方差分析检验,独立样本间比较采用SNK-q检验.结果 肠道组织TNF-α含量在HBO-I组最低,其次为HBO-P组(每两组比较P＜0.05),但前两组明显低于HBO-R组和I/R组(P＜0.05),HBO-R组略低于I/R组,但差异无统计学意义(P＞0.05);Caspase-3表达在HBO-I组最低,HBO-P组次之(两组比较P＜0.05);HBO-R和I/R组最高(与前两组比较P＜0.05),尽管HBO-R组略低于I/R组,但差异无统计学意义(P＞0.05);ATP含量在HBO-I组最低,HBO-P组次之(两组比较P＜0.05),HBO-R和I/R组最高(与前两组比较P＜0.05),尽管HBO-R组略低于I/R组,但差异无统计学意义(P＞0.05).结论 HBO、小肠I/R损伤和小肠黏膜上皮凋亡之间存在联系;HBO治疗可以维持黏膜上皮细胞能量代谢,减少ATP耗竭,降低肠道组织TNF-α含量,减轻I/R损伤小肠黏膜上皮凋亡;在缺血期和缺血前应用HBO治疗显示有益结果,特别是在缺血期应用HBO效果最好,再灌注期应用HBO无效.     

高压氧对重型颅脑损伤术后患者长期预后的影响

目的:探讨高压氧(HBO)对重型颅脑损伤开颅术后疗效及预后的影响。方法:重型颅脑损伤后行标准外伤大骨瓣开颅术后患者97例,术后接受HBO治疗3个月,按是否坚持完成HBO治疗分为完成组61例和未完成组36例。随访5年,观察2组并发癫痫的比率、癫痫发作周期、死亡人数、格拉斯哥昏迷量表(GCS)及生存质量指数(QLI)评分。结果:2组术后24h及术后3个月GCS评分均明显高于术前(P<0.05),术后3个月完成组GCS及QLI评分明显高于未完成组(P<0.05),完成组出现继发癫痫及死亡例数明显低于未完成组(P<0.05);癫痫患者发作周期明显长于未完成组(P<0.05)。结论:重型颅脑损伤患者行标准外伤大骨瓣开颅术后配合标准疗程的HBO治疗可明显降低继发癫痫的比率,提高生存质量。     

高压氧对鼠损伤脊髓内神经生长相关蛋白表达的影响

目的研究高压氧(HBO)治疗对脊髓损伤(SCI)组织中神经生长相关蛋白(GAP-43)表达水平的影响。方法用Allen氏WD法制作鼠脊髓损伤模型。55只成年Wistar鼠随机分为正常组、SCI对照组和HBO治疗组。治疗组于术后每天HBO治疗1次，对照组无特殊治疗：各组分别于术后1d、4d、7d、10d、14d各随机取鼠5只，取损伤脊髓组织，Western blot法检测GAP-43表达水平。结果GAP-43在正常成年鼠脊髓中少量表达，SCI后表达增加且HBO治疗组较对照组表达更为显著：术后1周时SCI对照组GAP-43表达达到高峰，2周时降至接近初始水平，但HBO治疗组GAP-43表达仍维持高水平。结论HBO可增强损伤脊髓组织GAP-43表达。