重组牛胰蛋白酶抑制剂对小鼠急性肝损伤的保护作用

目的观察重组牛胰蛋白酶抑制剂(rBPTI)对小鼠急性肝损伤的保护作用。方法小鼠60只随机分成6组:正常对照组、模型组、rBPTI的3个剂量组(分别为3、6、12×104kIU·kg-1)、抑肽酶组(6×104kIU·kg-1)。每天腹腔注射给药,7d后体外注射CCl4建立小鼠急性肝损伤模型。末次给药后眼眶取血测定小鼠血清ALT、AST活性,观察肝脏组织病理改变。结果各剂量rBPTI可不同程度降低小鼠血清ALT、AST活性,降低肝组织MDA含量,与模型组比较差异有统计学意义(P<0·05、P<0·01),同时不同程度减轻肝组织病理损伤。结论rBPTI对体外CCl4诱导的小鼠急性肝损伤具有保护作用,作用效果同天然BPTI相当。     

Effects of human urinary trypsin inhibitor against operative stress

Effects of human urinary trypsin inhibitor (MTI) against operative stress were investigated. Laparotomy in a mouse caused suppression of immunological functions such as phagocytic activity and antibody formation, followed by loss of resistivity to bacterial infection and acceleration of growth of concealed tumor. The operation also caused damages to the body such as enhancement of protein catabolism and suppression of renal function, followed by increase of blood urea nitrogen, increase of protease activity in skeletal muscle and suppression of PSP clearance. Since MTI wholly ameliorated these undesirable conditions of the body caused by operative stress, it was suggested that MTI has an effect on maintaining the homeostasis of the living body as well as the ability to inhibit trypsin.     

丙泊酚对内毒素休克兔的保护作用

目的探讨不同剂量丙泊酚对内毒素休克兔的保护作用。方法连续注射LPS复制内毒素休克模型,新西兰大白兔50只,雌雄不限,随机分为5组:正常对照组(A组);内毒素对照组(B组);丙泊酚2mg·kg-1·h-1组(C组);丙泊酚5mg·kg-1·h-1组(D组);丙泊酚10mg·kg-1·h-1组(E组)。C、D、E组均为LPS注入后30min后予丙泊酚持续静脉泵入。5h内观察动物的MAP、PaO2、pH,血清TNF-α。比较48h内存活率。结果与B组比较,C、D、E三组均能不同程度地逆转MAP的下降,降低血清TNF-α水平,降低死亡率(P<0·01或P<0·05)。结论丙泊酚对内毒素休克兔具有保护作用。不同剂量丙泊酚对内毒素休克兔的保护效果不尽相同,并非丙泊酚剂量越大就效果越好。     

Protective effects of cyclosporin-A in splanchnic artery occlusion shock

Cyclosporin A (CsA) is an immunosuppressant drug that inhibits nitric oxide (NO) synthase induction in vascular smooth muscle cells. Splanchnic artery occlusion (SAO) shock is a lethal type of shock characterized by a marked vascular dysfunction in which the L-arginine/nitric oxide pathway plays an important role. We investigated whether CsA exerts protective effects in SAO shock by interfering with the L-arginine/nitric oxide pathway. Male anaesthetized rats (n=156) were subjected to clamping of the splanchnic arteries for 45 min. This surgical procedure resulted in an irreversible state of shock (SAO shock). Sham operated animals were used as controls. SAO shocked rats had a decreased survival (86+/-6 min, while sham shocked rats survived more than 240 min), marked hypotension, increased serum levels of TNF-alpha, enhanced plasma nitrite/nitrate concentrations (75+/-7.1 microM; sham shocked rats=1.6+/-0.5 microM) and enhanced inducible NO synthase (iNOS) protein induction and activity in the aorta. Moreover aortic rings from shocked rats showed a marked hyporeactivity to phenylephrine (PE, 1 nM - 10 microM). CsA (0.25, 0.5 and 1 mg kg(-1), 5 min after reperfusion) increased survival rate (SAO+CsA=236+/-9 min following the highest dose), reverted the marked hypotension, reduced plasma nitrite/nitrate concentration (11+/-5.2 microM following the highest dose), restored to control values the hyporeactivity to PE, and blunted iNOS protein induction and activity in aortic rings. The present data indicate that in an experimental rat model CsA may have antishock properties related to inhibition of L-arginine/nitric oxide pathway.     

Inhibitory effect of human urinary trypsin inhibitor (urinastatin) on lysosomal thiol proteinases

Effects of human urinary trypsin inhibitor, urinastatin, a compound clinically prescribed for treatment of acute pancreatitis, on lysosomal thiol proteinases were studied. Urinastatin had inhibitory effect on the activities of cathepsins B and H in vitro. In the experimental acute pancreatitis induced by a closed duodenal loop, urinastatin prevented the enhancement of esterolytic activity and the activities of cathepsins B and H. Urinastatin also improved the activities of inhibitors of cathepsins B and H in the case of pancreatitis.     

南瓜胰蛋白酶抑制剂

南瓜胰蛋白酶抑制剂(CMTI)具有独特的结构特点和抑制机制。此文对丝氨酸蛋白酶抑制剂的分类和CMTI的分子结构特征、酶学特性以及生理功能等方面的研究进展做一介绍。     

卡维地洛抗实验性心律失常作用

目的　评价卡维地洛（ＣＶＤ）抗实验性心律失常作用,并与β受体阻断剂普萘洛尔（ＰＲＯ） 进行比较。方法　采用氯仿致小鼠室颤（ＶＦ） , 哇巴因、乌头碱致豚鼠、大鼠心律失常,肾上腺素致豚鼠心律失常, 以及结扎大鼠冠状动脉诱发心律失常等５ 种模型。结果　与溶媒对照组相比, ＣＶＤ１ ｍｇ·ｋｇ－１ 显著降低氯仿诱发的小鼠ＶＦ 发生率〔１８－７５ ％（３／１６） ｖｓ８１－２５％ （１３／１６）,Ｐ＜ ０－０１〕,此作用与ＰＲＯ 相似。１ ｍｇ·ｋｇ－１ ＣＶＤ 和ＰＲＯ 均显著提高致室早（ＶＥ） , 室速（ＶＴ）, ＶＦ, 心搏停止（ＣＡ） 所需哇巴因和乌头碱用量（ Ｐ＜０－０１ ｖｓ 溶剂对照组） ;ＣＶＤ 对抗哇巴因的致心律失常作用较等剂量ＰＲＯ 显著（ Ｐ＜ ０－０１ ,ＣＶＤ ｖｓ ＰＲＯ）。ＣＶＤ 剂量依赖性地显著缩短ｉｖ 肾上腺素４０ μｇ·ｋｇ－ １ 所致心律失常持续时间,有效减少结扎冠脉诱发的缺血性心律失常ＶＴ,ＶＦ,ＣＡ 的发生率并缩短ＶＴ 的持续时间。结论　ＣＶＤ 具有抗多种实验性心律失常作用,该作用在等剂量时至少与ＰＲＯ 相近,或强于ＰＲＯ。ＣＶＤ的这种作用最终将有益于接受其治疗的原发性高血压、冠心病、充血性心力衰竭患者     

乙酰半胱氨酸对内毒素性休克兔的保护作用

研究乙酰半胱氨酸对内毒素体克兔的治疗作用。方法以大肠杆菌内毒素复制内纱休克模型,并分为对照组和ＮＡＣ治疗组,对两组间的血压变化,乳酸,丙二醛及一氧化氮的浓度变化进行了比较。     

硫氮卓酮对失血性休克犬胰腺的保护作用及其机制的研究

杂种犬１１只，快速失血使平均动脉压达６．０ｋＰａ．维持９０ｍｉｎ，回输全部血液，２４０ｍｉｎ处死动物。硫氮卓酮（Ｄｉｌｔｉａｙｅｍ，Ｄｉｌ，ｎ＝６）组于休克３０ｍｉｎ时静脉输注Ｄｉｌ（６００１μｇ·ｋｇ－１．１５ｍｉｇ内输完）。休克组在相同时间输入等量生理盐水。结果显示，和休克组比较，Ｄｉｌ治疗能降低胰腺组织黄嘌呤氧化酶（ＸＯ）活性，减少脂质过氧化产物丙二醛生成，增加谷胱甘肽过氧化物酶、Ｃｕ－Ｚｎ超氧化物酶（Ｃｕ－ＺｎＳＯＤ）和Ｍｎ－ＳＯＤ活性。并减轻胰腺损伤程度。提示Ｄｉｌ能保护休克时的胰腺，其机制与减少自由基生成，增加自由基清除酶活性有关。     

尿胰蛋白酶抑制剂生产中病毒灭活工艺的效果观察

目的验证尿胰蛋白酶抑制剂(UTI)生产工艺中采用的60℃水浴10 h和乙醇处理3 h的病毒灭活效果。方法将Sindbis病毒、伪狂犬病毒(PRV)和脊髓灰质炎病毒(PV1)3种指示病毒分别加入不同的UTI原料样品中,进行60℃水浴10 h和乙醇处理3 h,处理不同时间后分别取样,用微量细胞病变法检测不同时间段样品中的病毒残留滴度。结果60℃水浴10 h可灭活(6.503±0.102)LgTCID50/mL的Sindbis病毒,灭活(6.42±0.158)LgTCID50/mL的PRV以及(6.587±0.061)LgTCID50/mL的PV1。乙醇处理3 h后可灭活(5.88±0.204)LgTCID50/mL的Sindbis病毒,灭活(6.378±0.268)LgTCID50/mL的PRV以及(5.963±0.118)LgTCID50/mL的PV1。经两种方法处理后的样品加入细胞经3代盲传均未见细胞病变(CPE)出现。结论UTI生产工艺中采用的60℃水浴10 h和乙醇处理3 h均可灭活所验证的3种指示病毒,灭活效果>6.0 LgTCID50/mL。     

胰蛋白酶抑制剂研究概况

胰蛋白酶抑制剂泛指具有抑制胰蛋白酶活性作用的一类物质 ,此文对其来源、结构与功能的关系、在基因工程方面的发展以及目前研究较多的肿瘤相关胰蛋白酶抑制剂近几年的研究概况进行了综述。     

Beneficial effects of a neutral protease inhibitor in traumatic shock

Eglin C is a polypeptide inhibitor of the neutral proteases elastase and cathepsin G. We have investigated its action in traumatic shock in rats. Eglin C (2 mg/kg) given following trauma prolonged survival time from 2.3 +/- 0.5 h to 3.6 +/- 0.4 h (p less than 0.05) in traumatized rats. Although eglin C treatment had no significant effect on the increase in plasma cathepsin D activity, eglin C administration significantly blunted plasma myocardial depressant factor (MDF) accumulation, 54 +/- 3 vs 79 +/- 8 U/ml (p less than 0.02). Our findings indicate a potential role for neutral proteases in toxic factor formation.     

Kunitz型胰蛋白酶抑制剂的研究进展

Kunitz型胰蛋白酶抑制剂属于典型丝氨酸蛋白酶抑制剂,其生理功能至少包括了保护储存蛋白、调节内源蛋白酶的活性、保护个体免受昆虫和病原体的侵害、抑制癌细胞侵袭扩散、抗炎、抗真菌等作用。并已经应用到了抗虫性转基因植物和临床疾病治疗中。     

Protective effects of thromboxane receptor blockade in splanchnic artery occlusion shock

Splanchnic artery occlusion (SAO) followed by release of the occlusive clamps produces circulatory shock characterized by an abrupt hypotension, cardiac depression and high lethality. We studied the effects of the thromboxane receptor antagonist, BM-13505, in rats during SAO shock. Anesthetized rats subjected to total occlusion of the celiac and superior mesenteric arteries for 40 minutes developed a severe shock state following reperfusion, usually resulting in death within 90-120 minutes of release of the occlusion. BM-13505 was started at reperfusion for 10 minutes. SAO shock rats treated with BM-13505 (1 mg/kg) maintained post-reperfusion mean arterial blood pressure (MABP) at significantly higher values compared to those receiving only the vehicle (0.9% NaCl). Treatment with BM-13505 attenuated the plasma activity of the lysosomal protease cathepsin D (p less than 0.05 from vehicle) and the plasma accumulation of free amino-nitrogen compounds (p less than 0.01 from vehicle). Furthermore, the plasma activity of a myocardial depressant factor was significantly lower in BM-13505 treated rats than in non-treated rats (p less than 0.01 from vehicle). SAO shock rats treated with BM-13505 also exhibited a higher survival rate than the vehicle group (75% vs. 20%). These results suggest an important role of thromboxane A2 in the pathophysiology of SAO shock.     

苄普地尔对实验性心肌缺血的保护作用

本文对我院合成的苄普地尔的抗心肌缺血作用作了实验研究。在家兔结扎左冠状动脉的前降支造成急性心肌梗塞中,Bep5mg·kg~(-1)和Pro1mg·kg~(-1)均能使ECG的∑ST,NST,NQ降低,与NS组比较P<0.01,ST段恢复至等电位线的时间提前.梗塞心肌占全心重量的百分比减少,CPK测定值比NS组降低。Iso诱发大白鼠心肌缺血的实验中.Bep5,10mg·kg~(-1)与Pro5mg·kg~(-1)均可使∑ST↑↓的总mV数减少,与NS组比较P<0.01,病理组织学检查心肌损伤亦减轻。     

Protective effects of antioxidants on experimental liver injuries

Protective effects of 14 kinds of antioxidant on liver injury induced by carbon tetrachloride (CCl4) were investigated in terms of serum enzyme activities and bilirubin concentration. Consequently, the significant protective effects were found in sesamol, ellagic acid, cysteamine and cysteine. These antioxidants clearly decreased the lipid peroxide in the liver tissue. The protective effects on CCl4-induced liver injury in vivo were independent of the inhibitory activities on lipid peroxidation in hepatic mitochondria fraction in vitro.     

平律复方抗实验性心律失常的作用及其机理研究

目的:研究平律复方(PL)抗实验性心律失常的作用,并初步探讨其作用机理。方法:采用氯仿、氯化钙以及心肌缺血再灌注三种心律失常动物模型,监测标准Ⅱ导联心电图;测定缺血再灌注大鼠血清肌酸激酶(CK)和乳酸脱氢酶(LDH)活性;放射配基受体结合法分析心肌组织血小板激活因子(plate-let activating factor,PAF)受体蛋白表达水平;RT-PCR法检测PAF受体mRNA表达水平;测定心肌脂质过氧化产物丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性。结果:PL(ig,0.04、0.20、1.00 g.kg-1)对氯仿引起的小鼠心室纤颤有一定的保护作用;能减少氯化钙致大鼠室颤的发生率,降低死亡率;可显著降低心肌缺血再灌注大鼠心律失常的发生率,缩短持续时间,与模型对照组比较,PL小、中、大剂量组心肌CK和LDH分别降低了35.4%、51.8%、57.5%和22.4%、34.4%、38.4%;剂量依赖性下调心肌细胞PAF受体蛋白及mRNA表达水平,升高心肌SOD活性、降低MDA含量。结论:PL对氯仿、氯化钙以及心肌缺血再灌注诱发的心律失常均有较好的保护作用,其作用机制可能与下调心肌细胞PAF受体水平,抑制脂质过氧化有关。     

Existence of a human urinary trypsin inhibitor (urinastatin)-like substance in the rat brain.

A human urinary trypsin inhibitor, urinastatin (UT)-like immunoreactive substance with trypsin inhibitory activity, was demonstrated in certain brain regions in rats, especially the cerebral cortex, hippocampus and hypothalamus. Although this UT-like substance in the rat brain displayed an N-terminal amino acid sequence similar to that of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), it did not show any GAPDH activity. These results indicate that the UT-like substance in the rat brain is a protein different from GAPDH and indicates a localized distribution within certain brain regions partly related to learning and memory.