清肺化痰汤灌胃治疗对急性胰腺炎大鼠相关肺损伤的作用

摘要 目的：探讨清肺化痰汤灌胃治疗对急性胰腺炎大鼠相关肺损伤的作用。方法：45只SD大鼠随机分为3 组-正常对照组(15只)、模型组(15只)、清肺化痰组(15只),模型组与清肺化痰组都建立了急性胰腺炎大鼠相关肺损伤模型,对照组仅开腹后轻翻胰腺组织后缝合。清肺化痰组在造模前2 h给予清肺化痰汤0.6 mL/100 g灌胃,对照组与模型组给予等量生理盐水灌胃。结果：模型组与清肺化痰组建模后24 h、36 h、48 h的血清淀粉酶、IL-6、IL-8水平都高于对照组(P<0.05),清肺化痰组低于模型组(P<0.05)。模型组与清肺化痰组建模后24 h、36 h、48 h的肺组织病理评分、Caspase-3蛋白相对表达水平高于对照组(P<0.05),清肺化痰组低于模型组(P<0.05)。结论：清肺化痰汤灌胃治疗急性胰腺炎大鼠相关肺损伤能调节肺脏细胞凋亡水平,抑制炎症因子的释放,从而减轻肺损伤,改善大鼠的病情。     

人脐带间充质干细胞对脊柱骨折大鼠愈合及神经功能的影响

摘要 目的：探讨人脐带间充质干细胞(Human umbilical cord mesenchymal stem cells,hUC-MSCs)对脊柱骨折大鼠愈合及神经功能的影响。方法：脊柱骨折Sprague-Dawley雄性大鼠模型30只随机分为hUC-MSCs组与对照组,各15只。hUC-MSCs组大鼠在骨折部位移植0.5 mL的hUC-MSCs(细胞浓度为2×10⁶/mL),对照组大鼠移植同体积的生理盐水,记录大鼠愈合及神经功能变化情况。结果：两组造模后15 min、30 min、90 min的平均动脉压都波动明显,不过组间对比差异无统计学意义(P>0.05)。与造模后2 w对比,两组造模后4 w的神经功能BBB评分均升高,且hUC-MSCs组造模后2 w、4 w的神经功能BBB评分都高于对照组(P<0.05)。hUC-MSCs组造模后8 w的骨体积分数高于对照组(P<0.05)。hUC-MSCs组骨折部位附近有少量骨痂生长,骨折线逐渐消失;骨痂已明显包裹骨折部位。hUC-MSCs组造模后8 w的脊髓细胞凋亡指数低于对照组(P<0.05)。结论：hUC-MSCs在脊柱骨折大鼠的应用能促进骨折愈合与改善神经功能,也可以抑制脊髓细胞凋亡,从而发挥很好的治疗作用。     

NLRP3炎症小体对克雷伯杆菌肺炎小鼠肺脏病理损伤的调节作用

摘要 目的：探讨含NLR家族PYRIN域蛋白3（NLR family pyrin domain containing 3,NLRP3）炎症小体对克雷伯杆菌肺炎小鼠肺脏病理损伤的调节作用。方法：56只C57BL/6小鼠随机平分为两组-模型组与对照组,模型组小鼠通过气管注射肺炎克雷伯杆菌建立克雷伯杆菌肺炎模型,对照组小鼠注射等体积的生理盐水,记录与观察肺脏病理损伤情况。结果：模型组建模第7 d与第14 d的肺泡灌洗液髓过氧化酶（Myeloperoxidase,MPO）活性都高于对照组（P<0.05）。模型组建模第7 d与第14 d的肺脏、脾脏、肝脏系数与肺脏病理评分、NLRP3蛋白相对表达水平都高于对照组（P<0.05）。在模型组中,建模第14 d的NLRP3蛋白相对表达水平与肺脏病理评分、肺脏系数、脾脏系数、肝脏系数、肺泡灌洗液MPO活性都存在正相关性（P<0.05）。结论：克雷伯杆菌肺炎小鼠NLRP3炎症小体呈现高表达状况,可介导小鼠肺脏病理损伤,促进MPO活性增加,加重多脏器损伤。     

原发性醛固酮增多症大鼠自主活动和学习记忆行为的影响

摘要 目的：探讨原发性醛固酮增多症(primary aldosteronism,PA)大鼠其自主活动和对学习记忆行为的影响。方法：8周龄健康雄SD(Sprague-Dawley)大鼠(n=30)随机分为对照组与模型组各15只。两组都皮下埋置微量渗透泵,模型组泵内灌注醛固酮,对照组泵内灌注等量的生理盐水,记录大鼠自主活动和学习记忆行为的变化情况。结果：所有大鼠均存活,模型组都造模成功,切口愈合良好。模型组造模后的收缩压高于对照组(P<0.05),也高于造模前(P<0.05),两组造模前后心率对比差异无统计学意义(P>0.05)。模型组造模后的逃避潜伏期与穿台次数少于对照组(P<0.05),也少于造模前(P<0.05)。模型组造模后的自主活动次数高于对照组(P<0.05),也高于造模前(P<0.05)。造模后模型组的鼠双微基因2(Mouse Double Microgene 2,MDM2)蛋白相对表达水平高于对照组(P<0.05)。造模后模型组的血清醛固酮含量都高对照组(P<0.05),血清钾离子、钠离子、肾素活性低于对照组(P<0.05)。结论：原发性醛固酮增多症大鼠伴随有血清钾离子、钠离子含量降低与MDM2蛋白的高表达,从而导致大鼠出现自主活动和学习记忆行为障碍。     

黄芩苷对慢性萎缩性胃炎模型鼠OPG/RANKL轴的影响

摘要 目的：探讨黄芩苷对慢性萎缩性胃炎模型鼠OPG/RANKL轴的影响。方法：将建模成功的大鼠(n=42)平分为三组-模型组、雷尼替丁组与黄芩苷组,黄芩苷组灌胃6.3 g/kg体重的黄芩苷溶液(5 mg?kg^-1),雷尼替丁组灌胃6.3 g/kg体重的雷尼替丁生理盐水溶液(150 mg?kg^-1),模型组灌胃与同容积的生理盐水,记录不同时间点OPG/RANKL轴表达变化情况。结果：雷尼替丁组与黄芩苷组治疗后2 w与4 w的体重高于模型组(P<0.05),黄芩苷组高于雷尼替丁组(P<0.05)。雷尼替丁组与黄芩苷组治疗后2 w与4 w的胃黏膜组织评分低于模型组(P<0.05),黄芩苷组低于雷尼替丁组(P<0.05)。雷尼替丁组与黄芩苷组治疗后2 w与4 w的血清NO与SOD含量高于模型组(P<0.05),黄芩苷组高于雷尼替丁组(P<0.05)。雷尼替丁组与黄芩苷组治疗后2 w与4 w的胃窦组织OPG、RANKL蛋白相对表达水平高于对照组,黄芩苷组高于雷尼替丁组(P<0.05)。结论：黄芩苷治疗慢性萎缩性胃炎模型鼠能激活OPG/RANKL轴,提高血清NO与SOD含量,能减少胃黏膜组织损伤,提高大鼠体重。     

康柏西普在糖尿病大鼠早期视网膜病变中的作用及对VEGF、ICAM-1及CRP的影响

摘要 目的：探讨康柏西普在糖尿病大鼠早期视网膜病变中的作用及对血管内皮生长因子 (vascular endothelial growth factor,VEGF)和细胞间粘附分子-1(Intercellular adhesion molecule-1,ICAM-1)及C-反应蛋白(C-reactive protein,CRP)的影响。方法：糖尿病大鼠早期视网膜病变模型(n=27)随机平分为三组-模型组、替米沙坦组与康柏西普组,造模成功后当天三组分别给予注射生理盐水、替米沙坦、康柏西普治疗,1次/w,持续4 w,检测VEGF、ICAM-1及CRP表达情况。结果：大鼠造模成功后均出现食欲增多、饮水、尿量、体重减轻的现象。替米沙坦组与康柏西普组治疗第1 w与第4 w的体重高于模型组(P<0.05),康柏西普组高于替米沙坦组(P<0.05)。替米沙坦组与康柏西普组治疗第1 w与第4 w的空腹血糖低于模型组(P<0.05),康柏西普组低于替米沙坦组(P<0.05)。替米沙坦组与康柏西普组治疗第4 w的视网膜VEGF、ICAM-1、CRP蛋白相对表达水平低于模型组(P<0.05),康柏西普组低于替米沙坦组(P<0.05)。康柏西普组视网膜厚度变薄不明显,内、外核层细胞排列整齐,神经纤维层未见明显空泡样变性。结论：康柏西普在糖尿病大鼠早期视网膜病变中的应用能抑制VEGF、ICAM-1及CRP的表达,能促进降低血糖,增加大鼠体重。     

电针对脓毒症大鼠肺炎症反应和高迁移率族蛋白B1的影响

摘要 目的：研究电针足三里对脓毒症大鼠肺脏炎症反应和病理损伤的调节,为脓毒症的临床治疗提供新的理论依据。方法：成年雄性SD大鼠40只,按照随机数字表法分为假手术组（sham组）、脓毒症（盲肠结扎穿刺术( Cecal ligation and puncture, CLP)组）、脓毒症+假电针组（非经非穴组）和脓毒症+电针足三里组（足三里组）,每组10只。除第一组外,其余大鼠均采用盲肠结扎穿孔术（CLP）制备脓毒症大鼠模型;造模前,脓毒症+假电针组选择非经非穴处电针刺激,脓毒症+电针足三里组给予足三里穴位电针处理,电针参数为疏密波,2 Hz,1 mA,持续30 min,连续5天。术后24 h,先取支气管肺泡灌洗液, 再取右肺测湿干重比,取左肺下叶观察病理学改变,取左肺上叶检测炎症因子肿瘤坏死因子-α(Tumor necrosis factor, TNF-α)、白介素-1(interleukin -1, IL-1β)、白介素-6(interleukin-6, IL-6)和HMGB1。结果：与sham组比较,CLP组大鼠肺组织出现明显病理损伤（均P＜0.05）,炎症因子明显升高（均P＜0.01）,高迁移率族蛋白1（High mobility group 1 protein, HMGB1）明显升高(P＜0.05);经过电针足三里处理,脓毒症大鼠肺组织病理损伤明显减轻（P＜0.05）,炎症因子明显降低（均P＜0.01）,HMGB1明显减少(P＜0.05)。CLP组与非经非穴组大鼠生存率、肺组织病理损伤、炎症因子和HMGB1无明显差异,差异无统计学意义（均P＞0.05）。结论：电针足三里可以减轻脓毒症大鼠肺的炎症反应和组织损伤,降低其肺脏HMGB1水平。     

内脂素对老年大鼠脑组织损伤和炎症反应的影响分析

摘要 目的：探讨与分析内脂素对老年大鼠脑组织损伤和炎症反应的影响。方法：10个月龄老年健康雄性Sprague-Dawley(SD)大鼠60只随机平分为两组-对照组与内脂素组,内脂素组给予腹腔注射重组人内脂素200 μg/次,对照组均给予等量蒸馏水灌胃,2次/w,连续给药4 w。对比两组给药前、给药第2 w、给药第4 w的逃避潜伏期、血清白介素(Interleukin,IL)-6与C-反应蛋白(C-reactive protein,CRP)含量,及给药第4 w的线粒体超氧化物歧化酶(Superoxide dismutase,SOD)与谷胱甘肽过氧化物酶(Glutathione peroxidase,GSH-Px)活性、海马与皮层区神经元凋亡率。结果：所有大鼠在实验期间均出现典型的绕池壁现象。两组给药前逃避潜伏期、血清IL-6与CRP含量对比差异无统计学意义(P>0.05),给药后两组第2 w、给药第4 w的逃避潜伏期、血清IL-6与CRP含量均降低(P<0.05),且内脂素组给药第2 w、给药第4 w的上述指标低于对照组,对比均有统计学意义(P<0.05);内脂素组给药第4 w的线粒体SOD、GSH-Px活性高于对照组,海马与皮层区神经元凋亡率低于对照组,经对比差异有统计学意义(P<0.05)。结论：内脂素在老年大鼠的应用能缓解脑组织损伤,抑制炎症反应,有利于清除过量的自由基,降低神经元的凋亡率。     

纤维调节素抑制脂多糖诱导性动物牙周炎的实验分析

摘要 目的：探讨与分析纤维调节素抑制脂多糖诱导性大鼠牙周炎的效果与机制。方法：将健康雌性Wistar大鼠36只平分为三组-对照组、牙周炎组与纤维调节素组。对照组给予正常喂养,不给予任何干预;牙周炎组与纤维调节素组都给予建立脂多糖诱导性牙周炎模型,建模后2 w纤维调节素组每天给予纤维调节素80 mg/kg?d,牙周炎组给予等体积的生理盐水灌胃治疗,持续4 w。结果：牙周炎组与纤维调节素组治疗第2 w与第4 w的牙龈指数、探诊深度、牙槽骨吸收值高于对照组(P<0.05),纤维调节素组低于牙周炎组(P<0.05)。牙周炎组与纤维调节素组治疗第2 w与第4 w的血清骨钙素(osteocalcin,OCN)值高于对照组(P<0.05),碱性磷酸酶(Alkaline phosphatase,ALP)值低于对照组(P<0.05),牙周炎组与纤维调节素组对比差异也都有统计学意义(P<0.05)。牙周炎组与纤维调节素组治疗第2 w与第4 w的蛋白酪氨酸磷酸酶-2(Src Homology Phosphotyrosyl Phosphatase 2,SHP-2)含蛋白相对表达水平高于对照组(P<0.05),纤维调节素组低于牙周炎组(P<0.05)。结论：纤维调节素可抑制脂多糖诱导性大鼠牙周炎的进展,抑制OCN与SHP-2蛋白的表达,促进ALP的表达,从而改善牙周炎大鼠的相关症状。     

七氟醚预处理介导AMPKα1通路对大鼠心肌缺血再灌注损伤的保护作用

摘要 目的：探讨七氟醚预处理介导腺苷酸环化激酶（AMP-activated protein kinase,AMPK）α1通路对大鼠心肌缺血再灌注损伤（myocardial ischemia-reperfusion injury, MIRI）的保护作用。方法：将清洁级雄性SD大鼠60只随机平分为三组：模型组、地佐辛组与七氟醚组,三组均建立MIRI模型。地佐辛组与模型组都在建模前24 h腹腔注射地佐辛40 μg/kg与等剂量生理盐水,七氟醚组吸入2.5 %七氟醚15 min。结果：所有大鼠在建模过程中均存活,无大鼠因严重并发症而舍弃。地佐辛组与七氟醚组再灌注后24 h与48 h的左心室收缩压、左心室舒张末期压、心肌梗死面积百分比、血清去甲肾上腺素含量、心脏组织AMPKα1和皮质激素调节激酶-1（glucocorticoid-regulated kinase-1,GK1）蛋白相对表达水平都低于模型组（P<0.05）,七氟醚组低于地佐辛组（P<0.05）。结论：七氟醚预处理可通过抑制大鼠MIRI的AMPKα1通路的激活和血清去甲肾上腺素释放,从而减少大鼠心肌梗死面积,并进一步促进心功能恢复正常。     

Effect of penehyclidine hydrochloride on expressions of MAPK in mice with CLP-induced acute lung injury

Penehyclidine hydrochloride (PHC) is a new anticholinergic drug. PHC has been shown to have a good curative effect for sepsis. Mitogen-activated protein kinase (MAPK) has recently been considered to play an important role in sepsis. In this study, the role of MAPK signal pathways in protective effects of PHC preconditioning on acute lung injury in cecal ligation and puncture (CLP)-induced sepsis was investigated. Healthy female mice were randomly divided into 4 groups: sham control, CLP, and 0.3 or 0.45 mg/kg PHC. At 12 h after surgery, arterial blood was drawn for blood gas analysis, and lung tissue samples were collected to examine pulmonary microvascular permeability, IL-6 levels and myeloperoxidase (MPO) activity. MAPK protein expressions were measured using western blot technique. Compared with sham control mice, acute lung injury was induced in CLP group, which was indicated by decreased PaO₂/FiO₂, increased pulmonary microvascular permeability, IL-6 levels and MPO activity. Furthermore, mice’ exposure to CLP induced the increased protein levels of MAPK. Treatment of 0.45 mg/kg PHC markedly improved PaO₂/FiO₂, decreased pulmonary microvascular permeability, IL-6 levels and MPO activity, and inhibited expressions of extracellular signal-regulated kinase (ERK1/2) and p38 MAPK. Taken together, these results suggest that PHC ameliorated acute lung injury through the inhibition of extracellular signal-regulated kinase (ERK1/2) and p38 MAPK activation in septic mice.     

急性出血坏死性胰腺炎肝损伤中TLR2, 4mRNA和蛋白的表达

目的:观察急性出血坏死性胰腺炎肝损伤中TLR-2、TLR4的表达水平,分析TLR2和TLR4在AHNP肝损伤中的表达意义。方法:48只成年Wistar大鼠作为实验动物,随机分为对照组和造模组各24只,造模组利用牛磺胆酸钠建立AHNP模型,在造模后3 h、12 h以及24 h时,每组分别各取8只大鼠,应用RT-PCR法检测TLR2、TLR4mRNA表达水平,应用Western blot检测肝脏组织中TLR2、TLR4蛋白表达水平。结果:造模后,造模组TLR2mRNA、TLR4mRNA、TLR2蛋白、TLR4蛋白显著升高,且在造模后12 h出现峰值,与同时段对照组相比差异显著(P0.01)。结论:急性出血坏死性胰腺炎肝损伤组织中TLR2、TLR4mRNA和蛋白表达水平异常升高,TLR2、TLR4可能参与了急性出血坏死性胰腺炎肝损伤发生发展过程。     

α2A-AR antagonism by BRL-44408 maleate attenuates acute lung injury in rats with downregulation of ERK1/2, p38MAPK,and p65 pathway

Acute respiratory distress syndrome (ARDS), characterized by acute hypoxic respiratory dysfunction or failure, is a manifestation of multiple organ failure in the lung, and the most common risk factor is sepsis. We previously showed that blocking α₂-adrenoceptor (α₂-AR) could attenuate lung injury induced by endotoxin in rats. α_2A-adrenoceptor (α_2A-AR), a subtype of α₂-AR plays a key role in inflammatory diseases, but the mechanism remains unknown. Here, we explored the effect of BRL-44408 maleate (BRL), a specific α_2A-AR antagonist, on cecal ligation puncture (CLP)-induced ARDS in rats and the underlying mechanism. Preadministration of BRL-44408 maleate significantly alleviated CLP-induced histological injury, macrophage infiltration, inflammatory response, and wet/dry ratio in lung tissue. However, there was no statistical difference in survival rate between the CLP and CLP+BRL groups. Extracellular regulated protein kinase (ERK1/2), p38MAPK, and p65 were activated in the CLP group, and BRL-44408 maleate inhibited the activation of these signal molecules, c-Jun N-terminal kinase (JNK) and protein kinase A (PKA) showed no changes in activation between these two groups. BRL-44408 maleate decreased lipopolysaccharide (LPS)-induced expression of cytokines in NR8383 rat alveolar macrophages and reduced phosphorylation of ERK1/2, p38MAPK, and p65. JNK and PKA were not influenced by LPS. Together, these findings suggest that antagonism of α_2A-AR improves CLP-induced acute lung injury and involves the downregulation of ERK1/2, p38MAPK, and p65 pathway independent of the activation of JNK and PKA.     

The effect of HMGB1 A box on lung injury in mice with acute pancreatitis

The objective of this study is to observe the effect of high-mobility group protein B1 A Box (HMGB1 A) box on lung injury in mice with acute pancreatitis and its effect on the level of high-mobility group protein B1 (HMGB1) in lung, to explore the mechanism. A total of 60 male Institute of Cancer Research mice were randomly divided into control group (n = 30) and treatment group (n = 30). Severe acute pancreatitis mice model was induced by 20% L-Arg intraperitoneal injection. The recombination HMGB1 A box was used in treatment after modeling. All the mice were killed under anesthesia at 24 and 48 h after the modeling injection. The level of HMGB1 and activity of myeloperoxidase (MPO) in lung were measured. The pathological changes of lung were observed. The level of HMGB1 in lung of A box treatment group decreased more significantly 24 h and 48 h after modeling compared with control group. The activity of MPO in lung of A box treatment group decreased more significantly 24 h after modeling compared with control group. The lung tissue pathologic score of A box treatment group decreased more significantly 48 h after modeling compared with control group. HMGB1 expression levels in the lungs were positively related to histological score of injured lung in acute pancreatitis. It indicates that HMGB1 A box is remarkably protective to lung injury induced by acute pancreatitis.     

胰腺p-STAT3在急性胰腺炎危重演变中的表达变化

目的：检测信号转导与转录激活因子3（STAT3）在不同程度胰腺炎模型小鼠胰腺组织中表达的变化,探讨其在急性胰腺炎危重演变中的作用。方法：48只健康雄性balb/c小鼠随机分为3组（n=16）：对照组（Con）、轻症急性胰腺炎（MAP）组、重症急性胰腺炎（SAP）组。Con组腹腔注射0.9% NaCl;MAP组腹腔注射雨蛙素;SAP组腹腔注射雨蛙素联合脂多糖;分别于造模后2 h、6 h检测血清淀粉酶的活性;分离胰腺、称重,计算胰腺湿重比;检测肺组织髓过氧化物酶（MPO）活性,评估炎细胞浸润肺组织的程度;HE染色切片,光镜下观察胰腺、肺组织病理学改变; Western blot法检测磷酸化STAT3（p-STAT3）的变化。结果：与Con组比较, MAP组和SAP组在各时间点血清淀粉酶活性和胰腺组织湿重比均升高（P<0.05）;肺组织MPO活性显著升高（P<0.05）,且SAP组肺MPO含量明显高于MAP组（P<0.01）。MAP组和SAP组,在造模后2 h,胰腺和肺均可见不同程度的病理学改变; SAP组在造模后2 h胰腺p-STAT3的表达最高,6 h表达有所减弱;MAP组各时间点仅有微量表达;Con组在各时间点为阴性表达。结论：p-STAT3在轻症急性胰腺炎和重症急性胰腺炎模型小鼠胰腺中的表达差异明显,说明重症急性胰腺炎的重症化与STAT3的活化关系密切;抑制STAT3活化将成为阻止急性胰腺炎重症化的靶点之一。     

Salvianolic acid B protects against acute lung injury by decreasing TRPM6 and TRPM7 expressions in a rat model of sepsis

This study aimed to investigate the protective effects of salvianolic acid B (SA‐B) on acute lung injury (ALI) through decreasing the expressions of channel kinase's TRPM6 and TRPM7. Wistar Septic rat models were established by lipopolysaccharide (LPS), which were separated into the control, lipopolysaccharide (LPS), SA‐B, SA‐B + si‐TRPM6, SA‐B + si‐TRPM7, si‐TRPM6, and si‐TRPM7 groups. Arterial blood gas, protein content, total white blood cell (WBC) count and the percentage of polymorphonuclear neutrophils (PMN%) were measured. Levels of TNF‐α and IL‐6 levels in bronchoalveolar lavage fluid (BALF) were monitored. Lung coefficient, myeloperoxidase (MPO) and superoxide dismutase (SOD) activity were conducted by MPO and SOD kit. The mRNA expressions of TRPM6 and TRPM7 were detected by qRT‐PCR. Compared with the control group, the PaO₂ and PaO₂/FiO₂ values exhibited decreases in other group, while the PaCO₂ value_, protein content, total WBC, PMN%, TNF‐α, IL‐6 levels and lung coefficient values all increased. MPO activity in lung tissue increased, while SOD activity decreased. TRPM6 and TRPM7 expressions increased significantly. Compared with the LPS group, the SA‐B, SA‐B + si‐TRPM6, SA‐B + si‐TRPM7, si‐TRPM6, and si‐TRPM7 groups had increased PaO₂ and the PaO₂/FiO₂, while decreased PaCO_2, protein content, total WBC, PMN%, TNF‐α, IL‐6 levels, and lung coefficient. MPO activity in lung tissue decreased while SOD activity increased. Decreased mRNA expressions of TRPM6 and TRPM7 in the SA‐B, SA‐B + si‐TRPM6, and SA‐B + si‐TRPM6 groups were observed. Through decreasing the expressions of the channel kinase TRPM6 and TRPM7, SA‐B protects against ALI in septic rats.     

Inhibition of Rho kinase by fasudil hydrochloride attenuates lung injury induced by intestinal ischemia and reperfusion

AimThe aim of this study is to evaluate the role of Rho-kinase in the pathogenesis of lung injury induced by intestinal ischemia/reperfusion (I/R) and the preconditioning effects of fasudil hydrochloride. The novel therapeutic approach of using Rho-kinase inhibitors in the treatment of intestinal I/R is introduced.MethodsSprague–Dawley (SD) rats were divided into 4 groups: intestinal I/R group, two fasudil pretreatment groups (7.5 mg/kg and 15 mg/kg), and controls. Intestinal and lung histopathology was evaluated; myeloperoxidase (MPO) and superoxide dismutase (SOD) levels in lung parenchyma were determined. Serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured. eNOS and P-ERM expression were measured by Western Blot.ResultsLung and intestinal injury were induced by intestinal I/R, characterized by histological damage and a significant increase in BALF protein. Compared to controls, serum TNF-α, IL-6, and lung MPO activity increased significantly in the I/R group, while SOD activity decreased. A strongly positive P-ERM expression was observed, while eNOS expression was weak. After fasudil administration, injury was ameliorated. Serum TNF-α, IL-6, lung MPO and P-ERM expression decreased significantly as compared to the I/R group, while SOD activity and eNOS expression increased significantly.SignificanceRho-kinase plays a key role in the pathogenesis of lung injury induced by intestinal I/R. The inhibition of the Rho-kinase pathway by fasudil hydrochloride may prevent lung injury.     

Treatment with antileukinate, a CXCR2 chemokine receptor antagonist, protects mice against acute pancreatitis and associated lung injury

Acute pancreatitis is a common, and as yet incurable, clinical condition, the incidence of which has been increasing over recent years. Chemokines are believed to play a key role in the pathogenesis of acute pancreatitis. We have earlier shown that treatment with a neutralizing antibody against CINC, a CXC chemokine, protects rats against acute pancreatitis-associated lung injury. The hexapeptide antileukinate (Ac-RRWWCR-NH2) is a potent inhibitor of binding of CXC chemokines to the receptors (CXCR2). This study aims to evaluate the effect of treatment with antileukinate on acute pancreatitis and the associated lung injury in mice. Acute pancreatitis was induced in adult male Swiss mice by hourly intra-peritoneal injections of caerulein (50 microg/kg/h) for 10 h. Antileukinate (52.63 mg/kg, s.c.) was administered to mice either 30 min before or 1 h after starting caerulein injections. Severity of acute pancreatitis was determined by measuring plasma amylase, pancreatic water content, pancreatic myeloperoxidase (MPO) activity, pancreatic macrophage inflammatory protein-2 (MIP-2) levels and histological examination of sections of pancreas. A rise in lung MPO activity and histological evidence of lung injury in lung sections was used as criteria for pancreatitis-associated lung injury. Treatment with antileukinate protected mice against acute pancreatitis and associated lung injury, showing thereby that anti-chemokine therapy may be of value in this condition.