川芎嗪对急性出血坏死性胰腺炎大鼠治疗作用及其机制的研究

观察川芎嗪对牛磺胆酸钠诱发的大鼠急性出血坏死性胰腺炎（ＡＨＮＰ）的治疗作用及其对血浆血栓素Ａ２（ＴＸＡ２）、前列环素（ＰＧＩ２）、血清脂质过氧化物（ＬＰＯ）、血清弹力蛋白酶抑制力（ＥＩＣ）的影响。结果表明，ＡＨＮＰ大鼠模型制备后，血浆ＴＸＡ２／ＰＧＩ２比值增高、血清ＬＰＯ值增加、ＥＩＣ降低；腹腔注射川芎嗪后，血清脂肪酶下降，腹水积聚减少，ＴＸＡ２／ＰＧＩ２比值稳定于正常水平，ＬＰＯ值降低，ＥＩＣ增高，胰腺出血坏死程度及腺泡细胞超微结构破坏减轻，大鼠存活率提高。提示川芎嗪对ＡＨＮＰ大鼠有一定治疗作用，此与其稳定ＴＸＡ２／ＰＧＩ２平衡、清除氧自由基及抑制胰弹性蛋白酶有关。     

血浆花生四烯酸代谢紊乱在大鼠急性胰腺炎肝脏损害发病机理中的作用

目的探讨急性胰腺炎肝脏受损与血浆花生四烯酸紊乱的关系．方法同时观察不同程度急性胰腺炎大鼠（ｎ＝１４０）肝脏受损情况和血浆花生四烯酸代谢产物血栓素Ｂ２（ＴＸＢ２）和６酮前列腺素Ｆ１α（６ｋｅｔｏＰＧＦ１α）的变化关系，并对急性胰腺炎时大鼠胰腺和肝脏组织病理学观察．结果发现急性出血坏死性胰腺炎大鼠肝脏发生明显病变，其程度与胰腺病理程度一致，急性出血坏死性胰腺炎时血浆ＴＸＢ２从对照组的１２１ｎｇ／Ｌ±２７ｎｇ／Ｌ上升至ＡＰ后２ｈ的３９９ｎｇ／Ｌ±１３１ｎｇ／Ｌ和４ｈ的６０７ｎｇ／Ｌ±１７４ｎｇ／Ｌ（Ｐ＜００１），ＴＸＢ２／６ｋｅｔｏＰＧＦ１α异常（Ｐ＜００１），而ＴＸＢ２／６ｋｅｔｏＰＧＦ１α比值变化与肝脏病理变化呈正相关（ｒｓ＝０８８９７，Ｐ＜００１）．通过异搏定治疗可明显改善胰腺病理损害和稳定血浆花生四烯酸代谢，明显减轻肝脏的损害．结论急性胰腺炎伴发的肝脏损害的发生发展与血浆花生四烯酸代谢紊乱有关     

前列环素及Dazmegrel对急性出血坏死性胰腺炎大鼠肺损伤的防治作用

前列环素及Ｄａｚｍｅｇｒｅｌ对急性出血坏死性胰腺炎大鼠肺损伤的防治作用王兴鹏徐家裕袁耀宗应用血栓素（ＴＸＡ＿２）合成酶抑制剂Ｄａｚｍｅｇｒｅｌ（Ｄａ）及外源性ＰＧＩ＿２调节ＴＸＡ＿２、ＰＧＩ＿２平衡，观察其对大鼠急性出血坏死性胰腺炎（ＡＨＮＰ）并发肺...     

急性出血坏死性胰腺炎犬血小板,纤溶功能的变化及四甲基吡嗪的作用

动态测定急性出血坏死性胰腺炎（ＡＨＮＰ）犬术后１、６、２４小时血浆ＧＭＰ－１４０、血小板电泳时间、ＰＡＩ和ｔ－ｐＡ活性，同时观察四甲基吡嗪（ＴＭＰ）对它们的影响。结果表明，ＡＨＮＰ犬、血浆ＧＭＦ－１４０含量、ＰＡＩ活性增高，血小板电泳时间延长，ｔ－ｐＡ活性降低，均较假手术组差异有显著性（Ｐ＜０．０５）；ＴＭＰ治疗组上述变化不显著。结果提示，犬ＡＨＮＰ早期血小板处于高度活化状态、纤溶功能降低，此可能与ＡＨＮＰ时胰腺微循环障碍、微血栓形成等病理生理现象的发生有关；ＴＭＰ可有效地纠正上述改变     

雷公藤多甙对大鼠急性肝衰竭的保护作用

目的探讨雷公藤多甙（ＧＴＷ）对实验性肝衰竭的保护作用．方法雄性Ｗｉｓｔａｒ大鼠２４只，随机分为对照组（ｎ＝８），急性肝衰竭（ＡＨＦ）组（ｎ＝８）和ＧＴＷ保护组（ｎ＝８）．ＧＴＷ组在实验前５ｄＧＴＷ２５ｍｇ／（ｋｇ·ｄ）经胃管灌胃，其余两组均以等量生理盐水溶液灌胃．从第６天开始，ＡＨＦ组和ＧＴＷ组均在空腹１２ｈ后ｉｐＤＧａｌＮ１６ｇ／ｋｇ，注射后４０ｈ，以３０ｇ／Ｌ戊巴比妥钠（４０ｍｇ／ｋｇ）ｉｐ麻醉，心脏抽血测定血清ＡＬＴ，ＴＢ和Ｔ淋巴细胞亚群．同时，在光镜和电镜下观察各组肝组织病理变化．结果ＡＨＦ组ＡＬＴ（ＩＵ／Ｌ）和ＴＢ（μｍｏｌ／Ｌ）分别为７８２８±５７６２和１２５６２７±６７０２７；ＯＸ８水平为１４０％±３％．ＧＴＷ组ＡＬＴ和ＴＢ分别为３５９±５４和４７±３５；ＯＸ８为４３％±４％．两组比较有显著统计学差异（Ｐ＜００５或００１）．同时，前者电镜下线粒体和内质网肿胀、破损，核内染色质凝聚，后者细胞器受损明显减轻．结论雷公藤多甙对实验性急性肝衰竭具有保护作用．     

内皮素与慢性肾小球肾炎及其水钠潴留关系探讨

检测了伴或不伴水钠潴留慢性肾炎患者血浆内皮素（ｐＥＴ）和２４ｈ尿蛋白排泄量。结果发现，水钠潴留组ｐＥＴ（１７２．４８±４５．７７μｇ／Ｌ）显著高于无水钠潴留组（１０２．３３±２２．８２μｇ／Ｌ，Ｐ＜０．０１）和对照组（９４．７５±２０．４８μｇ／Ｌ，ｐ＜０．０１）；２４ｈ尿蛋白排泄量，水钠潴留组显著高于无水钠潴留组（９．６２±７．２５ｇ／Ｌ２．７８±２．３３ｇ／Ｌ，Ｐ＜０．０１），但尿蛋白排泄量与ｐＥＴ水平无明显相关。提示ＥＴ可能参与了慢性肾炎水钠潴留的病理机理，并影响着慢性肾炎的病理发展。     

奥曲肽预防ERCP术后高淀粉酶血症及胰腺炎的疗效

目的探讨奥曲肽对内镜逆行胰胆管造影（ＥＲＣＰ）术后高淀粉酶血症及胰腺炎的预防作用．方法行ＥＲＣＰ患者２７６例，随机分为两组：预防组１６７例，分别于术前３０ｍｉｎ及术后４ｈ内ｓｃ奥曲肽０１ｍｇ；对照组１０９例，ＥＲＣＰ术前后分别予生理盐水１ｍＬｓｃ．两组患者术前后均不用其他任何抑制胰腺分泌及预防胰腺炎药物．并分别于术前、术后２ｈ，２４ｈ作血清淀粉酶测定，同时观察胰腺炎的发生情况．结果预防组ＥＲＣＰ术后２ｈ，２４ｈ血淀粉酶（Ｕ／Ｌ）分别为２４６±２２４和２５２±２９１；明显低于对照组（４９９±５９７和４６６±５５９，Ｐ＜００１）；预防组发生胰腺炎７例（４２％），对照组发生９例（８３％，Ｐ＜００１）．结论小剂量奥曲肽能有效地预防ＥＲＣＰ术后的高淀粉酶血症及胰腺炎     

肾上腺紧张素与高血压

目的观察实验性高血压大鼠及原发性高血压病（ＥＨ）患者的血浆肾上腺紧张素（ＡＤＴ）水平变化。方法用特异性放射免疫法测定血浆ＡＤＴ含量。结果两组实验性高血压大鼠平均动脉压（ＭＡＰ）及左室指数（ＬＶＩ）明显高于对照大鼠，而血浆ＡＤＴ水平则低于对照大鼠；５９例ＥＨ患者血浆ＡＤＴ水平（１０１．４３±４．１８ｎｇ／Ｌ）亦明显低于对照组（１６６．９３±５．０７ｎｇ／Ｌ，Ｐ＜０．００１），随着病期的加重，降低更显著，组间有显著差异（Ｆ＝７４．２９，Ｐ＜０．００１），两两比较Ｐ值均＜０．０１。结论ＡＤＴ的这种变化是维持机体自稳态调节的一种代偿机制     

雷抑素对大鼠移植肝Kupffer细胞的影响

目的探讨肝移植术前应用雷抑素对大鼠肝Ｋｕｐｆｅｒ细胞的影响方法以ＳＤ大鼠为供受体建立原位肝移植模型．受体移植术前３ｄ连续口服１％羧甲基纤维素１ｍｌ／ｄ（对照组）或雷抑素１０ｍｇ／ｋｇ·ｄ（用药组）．分别于术后１，２，３，２４ｈ采血并取肝组织，检测血清ＴＮＦ，ＡＬＴ及肝ＭＤＡ水平，观察肝超微结构及大鼠１周存活率变化．结果对照组移植术后３ｈ血清ＴＮＦ（５３ｋＵ／Ｌ±０４１ｋＵ／Ｌ），肝ＭＤＡ（４８４６ｎｍｏｌ／ｇ±２３６ｎｍｏｌ／ｇ）显著增加，ＴＮＦ表达呈强阳性；而且药组ＴＮＦ（０９ｋＵ／Ｌ±０１１ｋＵ／Ｌ）肝ＭＤＡ（３６１８ｎｍｏｌ／ｇ±１５４ｎｍｏｌ／ｇ）无明显变化，ＴＮＦ表达阴性，两者相差显著Ｐ＜００１）．电镜检查，对照组肝Ｋｕｐｆｅｒ细胞呈活化表现，而用药组肝Ｋｕｐｆｅｒ细胞呈非活化状态．对照及用药组术后１周存活率分别为０％和６０％．结论术前应用雷抑素可抑制移植肝ＴＮＦ和Ｏ２的产生，抑制Ｋｕｐｆｆｅｒ细胞活化，以减轻肝冷缺血再灌注损伤．     

原发性肝癌患者血清甲状腺激素变化

目的观察原发性肝癌（ＰＨＣ）患者血清甲状腺激素的变化。方法应用放射免疫法（ＲＩＡ）检测２４例ＰＨＣ患者的血清Ｔ３，Ｔ４，ＴＳＨ和ｒＴ３，并以２４例健康成人作对照。结果ＰＨＣ组血清Ｔ３为１．６０±０．１４ｎｍｏｌ／Ｌ，而对照组为２．３７±０．０８ｎｍｏｌ／Ｌ（Ｐ＜０．００１）。ＰＨＣ切除组血清Ｔ３，Ｔ４和ｒＴ３分别为１．９４±０．１６ｎｍｏｌ／Ｌ，１３４．３４±１１．４９ｎｍｏｌ／Ｌ和２．６１±０．３９；而ＰＣＨ未切除组分别为１．２２±０．１７ｎｍｏｌ／Ｌ（Ｐ＜０．０５），１０４．０１±７．２４ｎｍｏｌ／Ｌ（Ｐ＜０．０５）和１．３５±０．３６（Ｐ＜０．０５）。结论ＰＨＣ患者血清Ｔ３降低，晚期患者出现血清Ｔ４降低和Ｔ３／ｒＴ３比值降低。     

Experimental research on production and uptake sites of TNFalpha in rats with acute hemorrhagic necrotic pancreatitis

AIM:To determine the site of production and uptake of tumor necrotic factor alpha (TNFalpha),and evaluate the relationship between serum TNFalphaand pla-sma endotoxin (ET) in rats with acute hemorrhagic necrotic pancreatitis (AHNP).METHODS:Sprague Dawley rats were divided into AHNP group and control group (n = 12). AHNP model was induced by retrograde injection of 5% sodium taurocholate via pancreatic bile duct. The blood samples were obtained through portal vein 2 and 6 hours after the operation.RESULTS:The contents of TNFalphain portal vein were increased rapidly in the development of AHNP. They were lower in hepatic vein (280.59 plus minus 20.02) and femoral artery (310.82 plus minus 7.97) than in portal vein (354.91 plus minus 25.50) (P < 0.05), and higher in femoral artery than in hepatic vein 6 hours after the operation (P <0.05). TNFalphalevel in plasma was increased significantly when ET level in portal vein showed no increase. CONCLUSION: Pancreas, spleen, liver, intestinal tract and lung are the main organs to produce TNFalpha, and liver is also an important site for TNFalphauptake in the development of AHNP. Plasma endotoxin is not a trigger for TNFalpharelease in rats with AHNP.     

奥美拉唑对大鼠急性出血坏死性胰腺炎的保护作用

为探讨奥美拉唑(OM)对大鼠急性出血坏死性胰腺炎(AHNP)的保护作用,采用大鼠十二指肠结扎加用闭襻内胆汁注射法制备AHNP模型.并观察用药后病鼠胰腺病理学和血液生化学变化。以及提高生存率的效果 结果表明:OM3或9mg/kg可显著减轻AHNP大鼠胰腺组织炎性损害,明显降低血清淀粉酶及乳酸脱氢酶水平 提高生存率。结论:OM对大鼠实验性胆汁反流所致的ANHP具有明显保护作用 其机理尚不明.可能与降低胰酶活性,减轻组织坏死有关。     

导向大黄素脂质体治疗急性出血坏死性胰腺炎的实验研究

本文报道用自制的大黄素脂质体在实验性出血坏死性胰腺炎(AHNP)的动物模型中作导向治疗的研究。实验依据是大黄素经丙谷胺和脂质体包裹后注入动脉,结果其在胰组织中的浓度显著高于单纯大黄素,大鼠在胆胰管内注射5％牛磺胆酸钠造成AHNP后,随机分为脂质体治疗组(PE组)、善得定治疗组(S组),大黄素治疗组(E组)和生理盐水对照组(Na组)。另外还设立了假手术组(P组)以及正常对照组。治疗均于造模后15min经腹主动脉给药。观察指标包括腹水、血清脂肪酶和淀粉酶、胰腺病理及死亡率。结果示治疗3小时后,各治疗组血清和腹水酶水平均较Na组有显著差异。6小时后PE组的酶水平较E组有显著差异。病理改变方面,PE组的病变亦明显较轻。死亡率的比较亦示PE组的效果最好(62.5％比87.5％)。本文讨论中提出PE治疗,特别是动脉内给药有明显效果,同时指出所用的脂质体制剂并未引起任何毒副作用,说明磷脂酶A,对胰腺细胞并无毒性反应。     

血小板活化因子在急性胰腺炎大鼠并发肾损伤中病理生理作用

目的:本文旨在观察血小板活化因子在急性出血坏死性胰腺炎(AHNP)大鼠肾损伤发生中作用。方法:159只SD大鼠随机分三组:假手术组、AHNP非治疗组和AHNP BN(52021)治疗祖。采用胰管内注入5％牛磺胆酸钠溶液诱导大鼠AHNP,应用~(86)Rb组织摄取法测定肾脏相对血流量及组织灌注量,并测定血小板聚集率(PAgR)。结果:与非治疗组相比较,BN(52021)治疗组肾脏相对血流量、组织灌注量显著提高;PAgR下降;肾脏病理损害减轻。结论:血小板活化因子参与了急性出血坏死性胰腺炎大鼠肾损害的发生。     

重症胰腺炎二十碳烯酸类的异常代谢与大黄素、生长抑素的作用

重症胰腺炎(AHNP)胰组织出血、坏死被认为与二十碳烯酸类的异常代谢有关。在牛磺胆酸钠诱发大鼠AHNP模型,测定前列腺素E_1(PGE_2)、6-酮-前列腺素F_2(6-keto-PGF_2),血栓烷B_2(TXB_2)等变化,并以大黄素、生长抑素进行药物干预,以了解AHNP时二十碳烯酸类的异常代谢和上述药物的作用,结果显示,重症胰腺炎时血浆TXB_2显著增高,发病6小时达假手术组的4.5倍,而6-keto-PGF或PGE的测定值则呈降低趋势。应用大黄素或生长抑素后,TXB_2测定值显著降低,生长抑素组TXB_2测定值较之于大黄素组降低更为显著:6-keto-PGF_1和PGE_2则呈上升趋势。给药两组12小时生存率显著高于非治疗组:病理组织学评分及电镜超微结构观察示给药两组腺细胞坏死等病理损害减轻。作者认为,大黄素和生长抑素对AHNP时TXB_2等异常代谢有明显调整作用,与此相关的改善微循环和细胞保护机制可能是两药治疗AHNP的重要药理基础:联合应用大黄素与生长抑素可能会有协同作用。     

sPLA2抑制剂pku—mdl－101对大鼠急性出血坏死性胰腺炎肾损伤的治疗作用

目的探讨分泌型磷脂酶A2（sPLA2）抑制剂pku—mdl-101对急性出血坏死性胰腺炎（AHNP）相关肾损伤的治疗作用。方法18只Wistar大鼠随机分为假手术组（s0组）、AHNP组、抑制剂组,每组6只。后两组胆胰管逆行注射5％牛磺胆酸钠制备AHNP模型,抑制剂组给予pku-mdl－1015mg／kg。术后12h分批剖杀大鼠,测定各组血清淀粉酶、血肌酐（Cr）、肾组织sPLA2活性。RT-PCR法检测肾脏ⅡA型分泌型磷脂酶A2（sPLA2－ⅡA）mRNA,并取肾脏、胰腺组织行病理学检查。结果大鼠血清淀粉酶、Cr、肾组织sPLA2活性、sPIA2－ⅡA mRNA表达和肾脏、胰腺病理评分AHNP组均明显高于其他两组（P〈0．05）;抑制剂组均明显低于AHNP组（P〈0．05）,仍高于s0组（P均〈0．05）。结论pku－mdl－101能明显抑制sPLA2－ⅡA的表达,减轻大鼠急性出血坏死性胰腺炎相关性肾损伤。     

重症胰腺炎二十碳烯酸的异常代谢与大黄素,施他宁的作用

目的：探讨重症胰腺炎（AHNP）胰组织出血、坏死与二十碳烯酸类的异常代谢关系。方法：以牛黄胆酸钠诱发大鼠AHNP模型，测定前列腺素E2（PGE2）、6-酮-前列腺素F1a（6－keto－PGE1a）、血栓烷B2（TXB2）等变化，并以大黄素、施他宁药物干预，以了解AHNP时二十碳烯酸类的异常代谢和上述药物的作用。结果：重症胰腺炎时血浆TXB2显著增高．发病6小时达假手术组的4．5倍，而6－keto－PGF1a或PGE2的测定值则呈降低趋势．应用大黄素或施他宁后，TXB2测定值显著降低，施他宁组TXB2测定值较之于大黄素组降低更为显著；6－keto－PGE1a和PGE2则呈上升趋势．给药两组12小时生存率高于非治疗组；给药两组胰腺细胞坏死等病理损害减轻．结论：大黄素和施他宁对AHNP时TXB2等异常代谢有明显调整作用，与此相关的改善微循环和细胞保护机制可能是两药治疗AHNP的重要药理基础；联合应用大黄素与施他宁可能会有协同作用．     

Influence of splanchnic vascular infusion on the content of endotoxins in plasma and the translocation of intestinal bacteria in rats with acute hemorrhage necrosis pancreatitis

The main reason for the death of the patient with acute hemorrhage necrosis pancreatitis (AHNP) is pancreatic infection and multi-organ failure caused by endotoxemia and intestinal bacterial translocation[1-7]. However, the pathogenesis of endotoxemia and intestinal bacterial translocation remains a question[8-10]; moreover, no effective method of prevention and cure for it has been found till now[11 -15] In the present study, we infused low dose dopamine and low molecular weight dextran through the catheters to abdominal aorta and portal vein, and observed its influence on the endotoxin concentration in plasma and the rate of translocation of intestinal bacteria in AHNP rats.     

Effects of Ethanol and Naltrexone in a Model of Traumatic Brain Injury With Hemorrhagic Shock

BACKGROUND: Ethanol predisposes to traumatic injury and causes respiratory depression and cardiovascular compromise in models of traumatic brain injury (TBI) and hemorrhagic shock (HS). Endogenous opioids may play a role in ethanol intoxication and TBI. We studied the effects of ethanol and the opiate antagonist agent naltrexone (NTX) in a TBI/HS model. METHODS: Fifty-six pigs (20 kg) were anesthetized with isoflurane, intubated, instrumented, and subjected to fluid percussion TBI with concurrent 30 ml/kg hemorrhage over 30 min. Seven groups were studied: Control, EtOH, NTX, INJ, INJ/EtOH, INJ/NTX, and INJ/EtOH/NTX. Ethanol (2 g/kg IV) was given preinjury, followed by infusion of 0.4 g/kg/hr. NTX 0.3 mg/kg intravenous was given 5 min postinjury. Parameters monitored for 120 min postinjury included minute ventilation (VE), blood pressure (MAP), cerebral perfusion pressure (CPP), cerebral venous lactate (Lac), arterial and cerebral venous blood gases, and brain tissue PtiO2. RESULTS: Ethanol levels at injury were 220 mg/dL. Ethanol-treated animals had depression of hypercapnic ventilatory response, which was reversed by administration of naltrexone. MAP and CPP were significantly lower in injured animals, but were not significantly improved by NTX. Cerebral venous pH was lower and lactate was higher in ethanol-treated animals. CONCLUSION: In this TBI/HS model, NTX reverses ethanol-induced depression of hypercapnic ventilatory response but does not improve MAP, CPP, or metabolic acidosis. This suggests that the respiratory effects of ethanol in TBI, but not the hemodynamic effects, may be mediated by opiate receptor activation.     

Ulinastatin in the treatment of acute pancreatitis: A multicenter clinical trial

OBJECTIVE: To assess the effectiveness of Chinese‐made ulinastatin in the treatment of patients with acute edematous pancreatitis (AEP) and acute hemorrhagic and necrotic pancreatitis (AHNP). METHODS: A multicenter randomized controlled clinical trial was performed. Stratified by AHNP or AEP, patients were randomly allocated into either the treatment group (with ulinastatin) or the control group (treatment with cabexate or octreotide). Clinical symptoms and signs were scored as none, mild, moderate or severe. Laboratory tests included serum amylase, liver and renal function tests, routine blood tests, serum glucose, calcium, blood pH and PaO₂. Clinical results were assessed as cured, significantly effective, effective and non‐effective. All adverse effects were recorded. RESULTS: From April to July 2000, a total of 94 patients with acute pancreatitis were enrolled into the study (50 males; 44 females). In this patient group, there were 68 cases of mild pancreatitis and 26 cases of severe pancreatitis. The study showed that the global effective rates of ulinastatin and cabexate in treating AEP were 100%, whereas the cured rate for ulinastatin was 83.3%, which was a little higher than that for cabexate (71.4%), but this difference was not statistically significant. Clinical symptoms, such as abdominal pain and distension, almost disappeared within 3?5 days in both groups for both treatment protocols. The global effective rate of ulinastatin in treating AHNP was similar to that of octreotide (78.6 vs 81.9%; P= 0.840). The main complication in AHNP was pancreatic pseudocyst. Only one case showed increased levels of alanine aminotransferase. No adverse effects, including allergy, skin rash and decreases in the white blood cell count, were noted. No abnormalities in liver and renal function, electrolytes or routine blood tests were noted. CONCLUSIONS: Ulinastatin was shown to be effective in treating AEP and AHNP with few adverse effects.