Expression of heat shock protein 70 in lung tissuesof acute paraquat poisoned rats and interventionof ulinastatin

BACKGROUND： Paraquat （PQ） is an effective herbicide and is widely used in agricultural production, but PQ poisoning is frequently seen in humans with the lung as the target organ. Clinically pulmonary pathological changes are often used to predict the severity and prognosis of the patients. In this study, we observed the expression of heat shock protein 70 （HSP70） in rat lung after PQ poisoning and to investigate the therapeutic effects of ulinastatin.METHODS： Seventy-two adult healthy SD rats were randomly divided into a control group （group A, n=24）, a poisoning group （group B, n=24）, and an ulinastatin group （group C, n=24）. The rat models of acute PQ poisoning were established by intra-gastric administration of 80 mg/kg PQ to rats of groups B and C, and the rats of group C were intra-peritoneally injected with 100 000 IU/kg ulinastatin 30 minutes after poisoning. The expression of HSP70 in lung tissue was observed, and W/D and histopathological changes in the lung tissue were compared 12, 24, 48 and 72 hours after poisoning. The expression of HSP70 in the lung tissue was assayed by using RT-PCR. All quantitative data were processed with one-way analysis of variance to compare multiple sample means.RESULTS： Compared to group A, the expression of HSP70 in the lung of rats in groups B and C increased signi？ cantly at all intervals （P〈0.05）. The pathological changes in lung tissue of rats with PQ poisoning included congestion, leukocytes in？ ltration and local hemorrhage, whereas those of group C were signi？ cantly lessened.CONCLUSION： Ulinastatin may ameliorate acute lung injury to some extent after PQ poisoning in rats by enhancing the expression of HSP70.

乌司他丁对百草枯染毒大鼠肺组织热休克蛋白70和NF-κB的影响

目的 观察急性百草枯（paraquat,PQ）染毒大鼠肺组织中热休克蛋白70（hsp70）及NF-κB mRNA表达及乌司他丁（ulilnastatin,UTI）的作用.方法 将72只SD大鼠随机分为对照组、PQ组和UTI组,每组24只.染毒组：以80 mg/lg PQ一次性灌胃;治疗组：PQ灌胃后以UTI 10000 U/kg腹腔注射,每日1次.对照组一次性灌胃生理盐水.于12、24、48、72 h分别测定肺组织中髓过氧化物酶（MPO）活力,反转录-聚合酶链反应（RT-PCR）法测定肺组织中hsp70和NF-κB p65 mRNA的表达,观察大鼠肺组织病理变化.结果 PQ染毒后48 h内炎性细胞浸润明显,伴充血水肿;UTI组炎性细胞浸润较PQ染毒组少,充血水肿轻.染毒组大鼠肺组织中MPO活力在12、24、48、72 h分别为（31.72±6.42）、（56.23±8.63）、（87.21±10.02）、（107.21±13.52）U/g,UTI组12、24、48、72 h MPO活力分别为（15.65±3.21）、（35.98±5.74）、（59.33±9.65）、（71.25±10.58）U/g,较对照组[（11.38±1.25）U/g]明显升高,差异有统计学意义（P＜0.01）;UTI组MPO活力较染毒组明显降低,差异有统计学意义（P＜0.01）.UTI组12、24、48、72 h NF-κB p65 mRNA表达分别为0.3288±0.0147、0.5337±0.0328、0.7357±0.0424、0.7547±0.0905,与PQ组（分别为0.41 85±0.0294、0.8532±0.0841、0.9554±0.0975、1.0094±0.0703）比较,明显降低,差异有统计学意义（P＜0.01）.UTI组12、24、48、72 h hsp70 mRNA表达分别为0.5193±0.0254、0.8289±0.0606、0.7566±0.0277、0.4873±0.0105,与PQ组（分别为0.3897±0.0125、0.5904±0.0186、0.4007±0.0237、0.2293±0.0137）比较明显增加,差异有统计学意义（P＜0.01）.结论 大鼠急性PQ中毒后肺组织中hsp70、NF-κB p65 mRNA表达明显增高;UTI可以通过增加PQ中毒大鼠肺组织中HSP70表达,降低NF-κB表达,对肺脏起保护作用.

百草枯中毒大鼠肺组织热休克蛋白70表达及乌司他丁干预研究

目的 观察热休克蛋白70（HSP70）在百草枯（Paraquat PQ）中毒大鼠肺组织中表达及乌司他丁干预对其影响.方法 72只Spragne-Dawley（SD）大鼠随机（随机数字法）分为3组：空白对照组（A组）、染毒组（B组）和乌司他丁组（C组）,每组各24只.B组和C组PQ灌胃（80 mg/kg）染毒建立急性中毒模型.C组于PQ灌胃后30 min腹腔注射给UTI（10万U·kg-1·d-1）.观察染毒后12,24,48,72 h各组肺组织HSP70的表达、湿/干重比（W/D）和病理改变.HSP70采用逆转录聚合酶链反应（RT-PCR）测定.计量资料以均数±标准差（（x）±s）表示,组间单因素方差分析,结果以P＜0.05为差异有统计学意义.结果 与A组相比,各时间点B组和C组肺组织HSP70的表达明显增强,尤以C组为甚,差异有统计学意义.B组和C组肺组织病理检查可见PQ中毒后肺泡壁充血、炎性细胞浸润,并有局灶性出血.但C组病理改变较轻.结论 乌司他丁增强HSP70的表达,从而减轻PQ中毒大鼠急性肺损伤.

乌司他丁对糖尿病大鼠的肾脏保护作用及其机制

目的观察乌司他丁(UTI)对糖尿病大鼠肾脏的保护作用,并探讨其可能的机制。方法 Wistar大鼠30只,随机选10只为空白对照组(A组),余20只大鼠采用腹腔注射链脲佐菌素成功构建糖尿病模型后,随机分为糖尿病组(B组)及UTI干预组(C组),每组10只。C组每日腹腔注射UTI 40 000 IU/kg,A组及B组每日腹腔注射等量生理盐水。分别于第8周及第12周检测各组大鼠的空腹血糖(FPG)、24 h尿白蛋白、血肌酐(SCr)及尿肌酐,并计算内生肌酐清除率(Ccr);制备肾匀浆,并检测血清及肾匀浆丙二醛(MDA)、超氧化物歧化酶(SOD)、结缔组织生长因子(CTGF)、基质金属蛋白酶-9(MMP-9)及纤溶酶原激活物抑制剂-1(PAI-1)的含量。结果①B、C组FPG高于A组(P均<0.05),C组与B组间差异无统计学意义(P>0.05);②B、C组24 h尿白蛋白、SCr高于A组,C组低于B组(P均<0.05);③B、C组Ccr低于A组,C组高于B组(P均<0.05);④B、C组血清及肾匀浆MDA、CTGF及PAI-1含量均高于A组,C组低于B组(P均<0.05);⑤B、C组血清及肾匀浆SOD及MMP-9均低于A组,C组高于B组(P均<0.05)。结论 UTI对糖尿病大鼠肾功能具有保护作用,其机制可能与降低糖尿病大鼠MDA、CTGF及PAI-1表达、升高SOD及MMP-9表达,降低尿蛋白等因素有关。