p38 MAPK抑制剂对重症胰腺炎大鼠急性肺损伤的保护作用

目的探究p38MAPK抑制剂对重症胰腺炎大鼠急性肺损伤的保护作用。方法采用随机数字表法将60只大鼠分为三组,A组为假手术组,B组为重症胰腺炎模型组,C组为重症胰腺炎模型加p38MAPK抑制剂组;检测三组大鼠的肺组织病理学切片、肺组织湿干重比、髓过氧化物酶活性以及p38MAPK mRNA的表达水平。结果 B组大鼠与A组大鼠相比,其肺组织损伤病理评分、肺组织湿干重比、肺组织髓过氧化物酶(MPO)活性以及肺组织p38MAPK mRNA的表达水平均显著升高,而C组大鼠与B组大鼠相比上述指标均有所下降,P<0.05。结论 p38MAPK抑制剂能减少TNF-α的释放,降低炎症反应,为临床上治疗重症急性胰腺炎并发急性肺损伤的提供新的方向。     

罗格列酮对重症急性胰腺炎合并肺损伤的防治作用

目的 研究抵抗素在过氧化物酶增殖物激活受体(PPAR-γ)激动剂(罗格列酮)对大鼠重症急性胰腺炎(SAP)及其合并肺损伤防治中的作用及其作用机制.方法 用ELISA法检测大鼠血清淀粉酶(AMY)、抵抗素、肿瘤坏死因子(TNF-α)、白细胞介素-1β(IL-1β)和C.反应蛋白(CRP)的水平变化,检测肺组织髓过氧化物酶(MPO)、肺湿/干重比值、胰腺/体质量比值、胰腺和肺组织病理变化;免疫组化检测胰腺组织中抵抗素的表达;实时定量PCR法检测胰腺组织中抵抗素mRNA的水平.结果 罗格列酮预防组和治疗组大鼠血清AMY、抵抗素、TNF-α、IL-1B和CRP水平较SAP组均明显下降(均P＜0.01),预防组和治疗组与对照组相比均有明显升高(均P＜0.01),预防组和治疗组之间相比较有所变化,但两者之间无统计学意义;罗格列酮预防和治疗组胰腺/体质量比、胰腺病理评分、肺组织MPO含量和肺的病理评分较SAP组均明显降低(均P＜0.01);对照组、SAP组、预防组和治疗组大鼠的胰腺组织抵抗素mRNA相对表达量(RQ值)较SAP组明显降低(均P＜0.01),而与对照组相比较均明显升高(P＜0.01),但预防组与治疗组之间差异无统计学意义.结论 罗格列酮对SAP及合并肺损伤有明显的预防和治疗作用.     

乌司他丁对大鼠SAP肺损伤的保护作用

目的探讨大鼠重症急性胰腺炎(SAP)合并肺损伤的发病因素及乌司他丁对大鼠SAP合并肺损伤模型的保护作用。方法48只SD大鼠随机均分为三组:假手术组(S)、SAP组、乌司他丁治疗组(U),每组再分为术后6小时和12小时亚组。检测血AMY、TNF-α、MDA和肺MPO浓度并对胰、肺组织进行病理评分,比较U组给药后上述指标的变化。结果(1)U组血AMY、TNF-α、MDA和肺MPO浓度及胰、肺病理评分与同时点SAP组相比明显降低(P<0.05);(2)SAP组TNF-α在12小时比6小时明显下降(P<0.05);(3)血AMY、TNF-α、MDA和肺MPO浓度与胰、肺病理评分呈正相关(r=0.343~0.781,P<0.01)。结论(1)TNF-α、MDA和肺组织MPO是引起SAP合并肺损伤的重要因素,乌司他丁能减轻SAP合并肺损伤;(2)通过检测血AMY、TNF-α、MDA和肺MPO浓度可以间接地反映胰、肺损伤的程度。     

川芎嗪对大鼠急性坏死性胰腺炎肺损伤的保护作用

目的探讨微循环障碍在急性坏死性胰腺炎肺损伤中的作用,同时观察川芎嗪对胰腺炎肺损伤的干预效应。方法SD大鼠192只,随机均分为对照组(C)、胰腺炎组(P)、川芎嗪治疗组(T)。大鼠胰腺被膜下均匀注射5%牛磺胆酸钠4ml·kg-1,制作急性坏死性胰腺炎模型,C组胰腺被膜下注射等量生理盐水,T组经股静脉注射0.6%川芎嗪10ml·kg-1。每组中8只SD大鼠采用放射性生物微球技术,在制模后0.5、2.0、6.0、12.0h分别测定肺的血流量,另8只用于胰腺、肺的病理评分,以肺组织的过氧化酶(MPO)活性、肺湿/干重比作为衡量肺损伤的指标。结果P、C组相比,各时相肺脏的血流量均明显降低(P<0.05);各时相病理改变明显加重,时间越长,损害越重,其程度与血流量相关;肺干/湿明显加重,组织MPO活性明显增加(P<0.05或P<0.01)。T、P组相比,各时相肺的血流量较P组均明显降低(P<0.01);各时相病理改变明显减轻,肺干/湿无明显变化(P>0.05),组织MPO活性明显下降(P<0.05)。急性坏死性胰腺炎(ANP)时,肺组织血流量与肺湿/干重比率、肺组织MPO活性、肺组织损伤程度呈显著负相关。结论微循环障碍在急性坏死性胰腺炎的肺组织损伤中起着重要的作用。川芎嗪可以改善微循环,减轻胰腺及肺损害。     

丁酸钠对重症急性胰腺炎大鼠肺损伤的保护作用

目的探讨丁酸钠对大鼠重症急性胰腺炎（SAP）合并肺损伤的治疗作用。方法牛磺胆酸钠逆行胰胆管注射制作SAP动物模型,30只SD大鼠分成对照组、SAP组及丁酸钠（NaB）治疗组,检测胰腺湿/干重比值、胰腺及肺脏病理改变、肺脏细胞凋亡情况。结果 NaB治疗组肺组织湿/干重比值下降;NaB治疗组胰腺及肺组织病理改变明显减轻。NaB治疗组肺组织细胞凋亡指数显著高于SAP组。结论 NaB可以有效诱导SAP大鼠肺组织细胞发生凋亡,减轻肺损伤。     

白藜芦醇对大鼠重症急性胰腺炎肺损伤NF-κB活性影响的实验研究

目的探讨白藜芦醇对大鼠重症急性胰腺炎肺损伤时NF-κB活化的影响,以研究其对急性胰腺炎肺损伤的治疗作用及作用机制。方法 30只大鼠随机分为3组（n=10）：假手术组（SO）、重症急性胰腺炎模型组（SAP）、白藜芦醇治疗组（RES）。5%牛黄胆酸钠逆行胰胆管穿刺注射复制大鼠重症急性胰腺炎模型,尾静脉注射10g/L白藜芦醇悬混液（0.1ml/100g）,6h后处死大鼠,观测腹水量、血清淀粉酶、肺湿/干重比和肺组织病理学评分及NF-κB活性。结果 SAP组腹水量、血清淀粉酶、肺湿/干比重、病理学评分、NF-κB阳性率明显高于假手术组（P〈0.05）,RES组上述各项指标高于假手术组,但明显低于SAP组（P〈0.05）。结论白藜芦醇能减轻大鼠重症急性胰腺炎造成的肺损伤,对其有一定的治疗作用,其作用机制可能与抑制NF-κB的表达有关。     

急性胰腺炎相关性肺损伤模型的建立

目的采用5%牛磺胆酸钠逆行胰胆管注射建立急性出血坏死性胰腺炎(AHNP)大鼠模型,动态观察肺组织损伤情况,以评价能否建立有效的急性胰腺炎相关性肺损伤(APALI)动物实验模型。方法SD大鼠随机分成假手术对照组和AHNP模型组,动态观察3,6,12和24h四个时相点的血清淀粉酶、胰腺和肺病理组织学改变、肺组织湿干重比和髓过氧化物酶活性,伊文氏蓝法观察1.5,3和6h三个时相点肺血管通透性。结果血清淀粉酶、肺组织湿干重比和髓过氧化物酶活性在5%牛磺胆酸钠诱导后3h明显增高,并持续到24h,肺组织病理检查发现,牛磺胆酸钠诱导后肺组织就出现了明显的充血、出血、炎症细胞浸润、组织结构破坏等肺组织损伤的病理表现,AHNP大鼠1.5h肺血管通透性就显著增高,且随时间呈显著性增加,各指标与假手术组比较差异有显著性(P<0.05)。结论应用5%牛磺胆酸钠能够成功建立APALI大鼠模型,为进一步研究对APALI的防治作用奠定了基础。     

美常安对重症急性胰腺炎大鼠早期应用的影响

目的探讨微生态制剂早期应用对重症急性胰腺炎(SAP)大鼠血清TNF-α、IL-10、胰腺组织病理学改变。方法 60只SD大鼠随机分为3组,正常对照组,SAP模型组,微生态治疗组,用10%左旋精氨酸溶液腹腔内注射制作重症急性胰腺炎大鼠模型,采用放射免疫法检测大鼠血清TNF-α、IL-10浓度;观察胰腺组织湿干重比;光镜下评估胰腺组织病理学改变和胰腺病理组织学评分。结果 SAP模型组、微生态治疗组大鼠血清IL-10水平、胰腺湿干重比均明显高于正常对照组,P<0.05。治疗组胰腺湿干重比显著低于模型组,P<0.05,微生态治疗组大鼠血清IL-10水平高于模型组,P<0.01;而各组血清TNF-α水平有改变,但差异不具有统计学意义。结论美常安在重症急性胰腺炎大鼠早期应用观察中,明显提高SAP大鼠血清IL-10水平,促进抗炎因子产生,且可以减轻胰腺的病理组织学改变,进而减轻SAP的炎症反应,对SAP起到早期保护作用。     

前列腺素E1脂微球制剂对大鼠急性肺损伤的影响

目的:采用大鼠腹腔注射脂多糖(LPS)复制大鼠急性肺损伤(ALI)模型,评价前列腺素E1脂微球制剂(凯时)对急性肺损伤大鼠的保护作用。方法:雄性健康Sprague Dawley大鼠60只随机分为3组,A组:生理盐水组;B组:LPS模型组;C组:凯时治疗组。动物以硫喷妥纳腹腔注射麻醉,于实验3h分别测量每只大鼠的肺系数,肺通透指数,肺湿重/肺干重,肺组织中髓过氧化物酶(MPO)含量,丙二荃(MDA)和过氧化物歧化酶(SOD)的含量,血清细胞因子TNF-a、IL-12、IL10的浓度,肺组织中NF-KB蛋白的表达,并进行统计学分析。结果:①B组与A组比较,肺系数,肺通透指数,肺湿重/肺干重显著增加(P<0.05);血浆SOD含量,血清细胞因子IL10显著减少(P<0.05);肺组织中髓过氧化物(MPO)活性和丙二荃(MDA)含量,血清细胞因子TNF-a,IL-12显著增加(P<0.05)。②C组与B组比较,肺系数,肺通透指数,肺湿重/肺干重显著减少(P<0.05);肺组织SOD含量,血清细胞因子IL10显著升高(P<0.05);肺组织中髓过氧化物(MPO)活性和丙二荃(MDA)含量,血清细胞因子TNF-a,IL-12显著减少(P<0.05)。③C组与B组比较,NF-kB P65的表达明显低于A组(P<0.05)。结论:前列腺素E1脂微球制剂通过抑制NF-kB的表达,减少中性粒细胞的渗出,对LPS诱导的急性肺损伤大鼠有明显保护作用。     

罗格列酮对重症急性胰腺炎肺损伤保护作用的实验研究

【摘要】目的探讨罗格列酮对重症急性胰腺炎（SAP）肺损伤的保护作用。方法72只SD大鼠随机均分为假手术组（SO组）、SAP组及罗格列酮处理组（干预组）。分别观察各组大鼠血浆淀粉酶（AMY）、肿瘤坏死因子（TNF）-α、动脉血氧分压[p（O2）]、肺组织髓过氧化物酶（MPO）、肺湿/干比值的化及肺组织病理改变,免疫组化法及半定量逆转录聚合酶链反应（RT-PCR）法检测肺组织核因子（NF）-κB、TNF-αmRNA及细胞间黏附分子1（ICAM-1）mRNA的表达。结果SAP组AMY、TNF-α、MPO及肺组织NF-κB、TNF-αmRNA及ICAM-1mRNA表达较SO组显著增加(P<0.05）,干预组6h、12h肺组织湿/干比值较SAP组降低（P<0.05）,而动脉p（O2）较SAP组明显升高（P<0.05）,干预组各时点肺组织病理损伤较SAP组均明显减轻。结论罗格列酮可能通过抑制肺组织NF-κB的活性,减少肺组织TNF-α、ICAM-1的产生从而保护SAP合并肺损伤。     

大剂量呋塞米持续静脉泵入对早期急性肾损伤伴急性肺水肿的临床疗效

目的 研究大剂量呋塞米持续静脉泵入对早期急性肾损伤伴急性肺水肿的临床疗效。方法 选择2012年2月~2015年12月在陕西省人民医院进行诊治的早期急性肾损伤伴急性肺水肿患者180例,所有患者均先持续静脉泵入1~2 mg/min呋塞米,再按照患者尿量的多少调整呋塞米的用药剂量。分别在治疗前和治疗后6、12、24、48、72 h,观察并记录患者的血肌酐、血尿素氮、氧合指数、血钾、机械通气时间、pH值、预后情况和不良反应发生情况。结果 呋塞米用药剂量开始减少的时间平均为（12.15±3.12）h;呋塞米的应用时间平均为（46.31±4.89）h;治疗后各时间点患者的血肌酐、血尿素氮、氧合指数、pH值和血钾均与治疗前有明显差异（P<0.05）,且治疗后各时间点上述观察指标均有明显差异（P<0.05）;180例患者中,治疗后有161例肾功能恢复,占89.44%,呼吸困难的症状得到明显减轻,X线胸片发现肺水肿有明显好转,成功停止机械通气,机械通气时间平均为（35.28±11.37）h;在治疗过程中,180例患者血流动力学稳定,均未出现低血压、耳聋和耳鸣等不良反应。结论 给予大剂量呋塞米治疗早期急性肾损伤伴急性肺水肿,能明显增加尿量,改善肾功能、内环境紊乱和预后,提高救治成功率。     

Glutamine attenuates hyperoxia-induced acute lung injury in mice

1. Glutamine is an amino acid that is used to treat various diseases. Glutamine has been reported to have protective effects in human pulmonary epithelia-like cells exposed to hyperoxia. However, the effects of glutamine in hyperoxia-induced lung injury have not been investigated in vivo .
2. Mice treated with saline or glutamine [(750 mg/kg) intravenously] were randomly exposed to hyperoxia for 48 or 72 h. Control mice treated with saline or glutamine were exposed to room air. Cytokine levels in bronchoalveolar lavage fluid (BALF), heat shock protein (HSP) 70, the wet/dry (W/D) weight ratio, malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity and pathoglogical findings in lung tissue were evaluated to determine the effects of glutamine on acute lung injury. In addition, survival was monitored.
3. Lung expression of HSP70 was significantly enhanced in both the control (room air) and 48 and 72 h hyperoxic glutamine-treated mice. The W/D ratio, BALF concentrations of tumour necrosis factor-α and interleukin-6, MDA levels, MPO activity, neutrophil infiltration and interstitial oedema in lung tissue were significantly lower at 48 and 72 h of hyperoxia in glutamine-treated mice compared with saline-treated mice.
4. In a separate series of experiments evaluating survival, after 96 h continuous exposure to hyperoxia, all saline-treated mice died. In contrast, all glutamine-treated mice died after 108 h exposure to hyperoxia.
5. The data suggest that glutamine administered to mice during hyperoxia has a protective effect against hyperoxia-induced acute lung injury and improves survival.     

Protective effects of pravastatin in murine lipopolysaccharide-induced acute lung injury

1. The present study was designed to determine whether pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, could attenuate acute lung injury (ALI) induced by lipopolysaccharide (LPS) in BALB/c mice. 2. Acute lung injury was induced successfully by intratracheal administraiton of LPS (3 microg/g) in BALB/c mice. Pravastatin (3, 10 and 30 mg/kg, i.p.) was administered to mice 24 h prior to and then again concomitant with LPS exposure. 3. Challenge with LPS alone produced a significant increase in lung index and the wet/dry weight ratio compared with control animals. Pulmonary microvascular leakage, as indicated by albumin content in the bronchoalveolar lavage fluid (BALF) and extravasation of Evans blue dye albumin into lung tissue, was apparently increased in LPS-exposed mice. Lipopolysaccharide exposure also produced a significant lung inflammatory response, reflected by myeloperoxidase activity and inflammatory cell counts in BALF. Furthermore, histological examination showed that mice exposed to LPS also exhibited prominent inflammatory cell infiltration and occasional alveolar haemorrhage. 4. Pravastatin (3, 10 or 30 mg/kg, i.p.) produced a significant reduction in multiple indices of LPS-induced pulmonary vascular leak and inflammatory cell infiltration into lung tissue. Elevated tumour necrosis factor (TNF)-alpha levels in lung tissue homogenates of ALI mice were significantly decreased after administration of 10 or 30 mg/kg pravastatin. 5. These findings confirm significant protection by pravastatin against LPS-induced lung vascular leak and inflammation and implicate a potential role for statins in the management of ALI. The inhibitory effect of pravastatin was associated with its effect in decreasing TNF-alpha.     

脓毒症相关性急性肺损伤发病机制研究进展

急性肺损伤/急性呼吸窘迫综合征（ALI/ARDS）是临床上常见的危重病之一,病因多、影响因素复杂、救治困难,病死率高。脓毒症是危重病最主要的死亡原因,也是引起ALI/ARDS的最常见的病因,尽管对脓毒症致ALI/ARDS的机制研究较多,其确切机制尚不完全清楚。本文就脓毒症致急性肺损伤的发病机制进行综述。     

前列腺素E1对急性肺损伤患者的作用

目的观察前列腺素E1对ALI患者的疗效.方法ICU收治的ALI患者46例,随机分为对照组和治疗组,在常规治疗的基础上,治疗组加用前列腺素E1,观测两组患者治疗前、治疗后72h的血气分析指标并分别计算氧合指数,比较1周后的有效率.结果前列腺E1能明显提高ALI患者的PaO2、SaO2和氧合指数(P＜0.01).总有效率达82.6%.结论前列腺素E1能有效提高ALI患者的氧合功能,为一种治疗ALI的理想药物.     

热休克蛋白70在大鼠急性肺损伤中的表达

目的:探讨急性肺损伤(ALI)大鼠肺组织热休克蛋白70(HSP70)的表达。方法:雌性Wistar大鼠36只,随机分为两组:急性肺损伤组(A组)、对照组(B组),大鼠尾静脉注射脂多糖(LPS)复制ALI模型。所有的动物于注射LPS后2,4,6 h处死,测定肺组织HSP70的表达、超氧化物歧化酶(SOD)活性及丙二醛(MDA)的含量。结果:A组同B组相比,各时间点肺组织HSP70表达均增多,以2,6 h升高明显(P<0.01),MDA含量增高(P<0.05),SOD活性明显降低(P<0.05)。结论:HSP70在ALI后的表达增多可能与其参与LPS所致肺损伤后的组织保护有关。     

芸香苷对实验性急性胰腺炎肺损伤的保护作用及机制

目的探讨芸香苷(rutoside,Ru)对实验性急性胰腺炎(AP)肺损伤的保护作用及机制。方法牛磺胆酸钠(STC)逆行胆胰管注射诱发大鼠AP模型后,立即按Ru15、30、60mg.kg-1.h-13个剂量持续静脉输注6h,观察AP大鼠动脉血气分析、肺湿重/干重比值、肺组织病理学、肺TNF-α、ICAM-1、NF-κB表达的变化。结果60mg.kg-1剂量组可升高AP大鼠降低的动脉PO2;Ru30、60mg.kg-1剂量组可降低肺湿/干重比值,同时可以改善肺病理损伤情况;Ru15、30、60mg.kg-1剂量组均可降低肺TNF-α、ICAM-1、NF-κB的表达。结论静脉输注Ru对实验性AP胰外肺损伤具有一定的保护作用,其发挥保护作用的机制可能与降低TNF-α、ICAM-1、NF-κB的表达有关。     

Baicalin attenuates air embolism-induced acute lung injury in rat isolated lungs

Background and purpose

Baicalin has been reported to have anti-inflammatory effects and protect against various tissue injuries. However, the effect of baicalin on air embolism-induced acute lung injury has not been tested yet.

Experimental approach

Acute lung injury was induced by infusion of air at a rate of 0.25 mL·min⁻¹ for 1 min into the pulmonary artery of rat isolated lungs. At the end of the experiment, samples were collected for assessment of lung injury, biochemical analysis and histology. Different doses of baicalin (1, 2 and 4 mg·kg⁻¹) were given into the perfusate before air infusion.

Key results

Air embolism elicited a significant increase in microvascular permeability (K_f), lung weight gain, wet/dry weight ratio, pulmonary artery pressure and protein concentration in the bronchoalveolar lavage fluid. Levels of the cytokines, tumour necrosis factor α and cytokine-induced neutrophil chemoattractant-1 in perfusate, and malondialdehyde levels and myeloperoxidase activities in lung tissue were also significantly increased. In addition, histological examination showed increased neutrophil infiltration in lung tissues. Furthermore, nuclear factor-κB activity and degradation of IκB-α were significantly increased in lungs. Pretreatment of the lungs with baicalin (4 mg·kg⁻¹) showed a statistically significant difference in all of the assessed parameters, except for alteration in the pulmonary artery pressure.

Conclusions and implications

Our study suggests that baicalin attenuated air embolism-induced acute lung injury and may be considered a useful adjunct drug therapy in this clinical condition.     

血管紧张素转换酶2在SARS病理途径中的作用

人类严重急性呼吸综合征(SARS)相关冠状病毒(SARS-CoV)感染导致的严重急性呼吸系统病变,其临床肺部病理损害特征与急性肺损伤和急性呼吸窘迫病变相似。SARS-CoV可以结合人血管紧张素转换酶(ACE)2,二者结合效率与病毒感染复制能力相关。ACE2与ACE1共同调控肾素-血管紧张素系统,二者的功能平衡维持肺的正常功能。SARS-CoV感染时,其棘突蛋白与ACE2结合,下调人体ACE2水平,肺内ACE2和ACE1功能失衡,血管紧张素Ⅱ过度激活AT1受体,导致肺部毛细血管通透性增加,随之出现肺水肿和急性肺损伤。ACE2是SARS病理途径中的关键因子,在SARS临床治疗和SARS药物研制中有重要意义。