一氧化碳抑制剂治疗感染性休克的实验研究

目的由血红素氧合酶(HO)催化血红素分解代谢而形成的一氧化碳(CO)可能作为一种新的内源性介质参与感染性休克一系列病理生理过程.方法本文应用实验家兔注射内毒素所致感染性休克模型,观察CO在感染性休克病程中的变化以及HO抑制剂锌原卟啉的疗效.结果血浆CO水平于内毒素注射后迅速增高,应用HO抑制剂锌原卟啉能显著抑制血浆CO水平的增高,并可显著减轻内毒素所致的血压降低和代谢性酸中毒程度.结论 HO抑制剂治疗感染性休克的临床价值值得深入研究.     

内源性CO/NO在内毒素休克大鼠主动脉低收缩反应中的介导作用

目的：探讨血红素－HO－CO－cGMP和L－精氨酸－NOS－NO－cGMP通路对内毒素休克（ES）大鼠主动脉血管张力的影响。方法：SD大鼠12只，分为LPS组和对照组，用离体血管环张力测定技术，观察胸主动脉环（TARs）对苯肾上腺素（PE）累积收缩反应，并分别用正铁血红素（He),L-精氨酸（L－Arg),锌原卟啉（ZnPP-IX)，氨基胍（AG），N－硝基－L－精氨酸（L－NNA）或亚甲蓝（MB）与TARs共同孵育20min后，比较两组对PE的收缩反应，动脉组织中CO／NO的含量，HO－1和NOS活性。结果：LPS组主动脉对PE累积收缩反应明显降低，用ZnPP-IX或AG孵育后，可部分逆转低血管反应性，经L－NNA或MB孵育，可完全逆转低血管反应，而且He或L－Arg孵育可不同程度加重低血管反应状态，LPS组动脉组织中CO／NO的含量明显上升，HO－1／NOS活性显著增加，结论：LPS可激活HO－1和iNOS，大量增加CO／NO合成，cGMP水平上升，共同介导ES大鼠主动脉低收缩反应。     

内源性一氧化碳对大鼠主动脉球囊损伤后新生内膜形成及丝裂素活化蛋白激酶活性的影响

目的：探讨内源性血红素加氧酶（ｈｅｍｅｏｘｙｇｅｎａｓｅ,ＨＯ）／ 一氧化碳（ｃａｒｂｏｎ ｍｏｎｏｘｉｄｅ,ＣＯ） 系统对大鼠主动脉球囊损伤后新生内膜形成及丝裂素活化蛋白激酶（ｍｉｔｏｇｅｎａｃｔｉｖａｔｅｄ ｐｒｏｔｅｉｎ ｋｉｎａｓｅ, ＭＡＰＫ） 激活的调节作用。方法：采用大鼠主动脉内膜球囊拉伤模型,观察ＨＯ 抑制剂锌卟啉９（ｚｉｎｃ ｐｒｏｔｏｐｏｒｐｈｙｒｉｎＩＸ,ＺｎＰＰ９）或其底物血红素左旋赖氨酸盐（ｈｅｍｅＬｌｙｓｉｎａｔｅ,ＨＬＬ）对血管壁细胞３ＨＴｄＲ掺入和ＭＡＰＫ 活性的影响,同时观察血管平滑肌ＨＯ活性和ＣＯ 生成的变化。结果：内膜拉伤后２ 周血管３ＨＴｄＲ 掺入和ＭＡＰＫ 活性明显增加,同时ＨＯ 活性和ＣＯ 的产生增加;ＺｎＰＰ９ 使血管的３ＨＴｄＲ掺入和ＭＡＰＫ 活性增加更为明显（ 分别比单独拉伤组增加３４ ．６％ 和３９．２％ ,均为Ｐ＜ ０．０１） ;而ＨＬＬ 使血管的３ＨＴｄＲ 掺入和ＭＡＰＫ 活性则明显降低（ 比单独拉伤组分别减少２９．４５ ％ 和３３．６ ％ ,均为Ｐ＜ ０．０１） 。结论：ＨＯ 活性上调或ＣＯ 产生增加是血管对机械拉伤的一种保护性应激反应;内源性ＨＯ／ＣＯ 系统直接     

缺氧时肺动脉平滑肌细胞血红素氧合酶/一氧化碳系统的变化及其对Ⅰ型胶原的影响

目的 :研究缺氧时大鼠肺动脉平滑肌细胞 (PASMC)诱导型血红素氧合酶 (HO 1 ) /一氧化碳 (CO)系统的变化及其对胶原合成的影响 ,探讨血红素氧合酶 /一氧化碳 (HO/CO)系统对缺氧性肺血管重建中胶原代谢的作用及其机制。方法 :原代培养的大鼠PASMC ,用分光光度计检测PASMC培养液中CO相对含量的变化 ,Westernblot检测PASMCHO 1和转化生长因子 β3 (TGF β3 )表达的变化 ,用免疫细胞化学法分别观察PASMCHO 1、TGF β3 、Ⅰ型胶原蛋白表达的变化 ,原位杂交法检测Ⅰ型前胶原mRNA表达的变化。结果 :缺氧 2 4h诱导PASMC表达TGF β3 、Ⅰ型胶原蛋白和mRNA ,与对照组比较缺氧使HO 1蛋白表达增加 6 7.4 5 % (P <0 .0 1 )、CO含量增加35 .4 1 % (P <0 .0 5 )。ZnPP(HO 1抑制剂 )使缺氧 2 4h大鼠PASMC的CO含量降低 7.88% (P <0 .0 1 )、HO 1蛋白表达减少 2 3.9% (P <0 .0 5 )、TGF β3 蛋白表达增高 393% (P <0 .0 1 )、Ⅰ型胶原蛋白和mRNA表达均增加。Hemin(HO 1诱导剂 )使缺氧 2 4h大鼠PASMC的CO含量增加 8.83% (P <0 .0 1 )、HO 1表达增高 1 0 5 % (P <0 .0 5 )、TGF β3 蛋白表达降低 6 8.1 2 % (P <0 .0 1 ) ,Ⅰ型胶原蛋白和mRNA表达均减少。结论 :缺氧刺激下大鼠PASMCHO/CO系统上调 ,内源性CO能够抑制Ⅰ型胶原     

低氧培养的PC12细胞凋亡的研究

目的研究PCI2细胞在低氧状态下,内源性一氧化碳（CO）的生成及其导致细胞凋亡的作用。方法将PCI2细胞分为常氧对照组（C组）、低氧组（H组）和低氧加血红素氧合酶（HO）抑制剂卟啉锌-9组（H＋ZnPP组）。检测2h时间点PCI2细胞血红素氧合酶的表达及内源性CO水平和细胞凋亡率。结果氧应激状态下,HO-1明显表达,HO-2无表达;H组HO水平与C组、H＋ZnPP组比较明显升高（P〈0．01）,H＋ZnPP组的HO水平高于C组（P〈0．01）;内源性CO水平以及细胞凋亡率与C组、H＋ZnPP组比较均明显升高（P〈0．01）。结论低氧状态下,PCI2细胞表面HO-1高表达,HO-2无明显表达,PC12细胞的凋亡率与内源性CO的水平密切相关,提示HO／内源性CO可能导致细胞凋亡的发生。     

Protective effect of heme oxygenase-1 on lung injury induced

Background Intratracheal instillation of blood induces self-repaired acute lung injury. However, the mechanism of repair has been unclear. Heme-oxygenase （HO）-1, which catalyzes heme breakdown, acts as an inducible defense against oxidative stress and plays an important role in inflammation. The objective of this study was to test the role of HO-1 in lung injury caused by intratracheal instillation of red cells. Methods Forty healthy, male Sprague-Dawley rats were randomly divided into five groups： normal group, saline group, erythrocyte group, erythrocyte＋zinc-protoporphyrin （ZnPP, HO-1 inhibitor） group and saline＋ZnPP group. At 2 days after intratracheal instillation of red cells, lung tissues and lavage samples were isolated for biochemical determinations and histological measurements. Results Histological analysis revealed that administration of ZnPP worsened the acute lung injury induced by instilled erythrocytes. HO-1 was over-expressed in the erythrocyte group and in the erythrocyte ＋ ZnPP group. Compared with the erythrocyte ＋ ZnPP group, the levels of total protein, lactate dehydrogenase and tumor necrosis factor-a in the lavage were lower （P 〈0.01）, while the level of interleukin-10 was higher in the erythrocyte group （P 〈0.01）. Conclusion HO-1 protects against erythrocyte-induced inflammatory injury in lung.     

血红素氧合酶-1的诱导对肺缺血再灌注损伤的保护作用

目的探讨血红素氧合酶-1的诱导对肺缺血再灌注损伤的保护作用。方法将40只健康Sprague-Dawley大鼠随机分为4组：假手术对照（sham）组、肺缺血再灌注（I／R）组（阻断左肺门30min再灌注2h）、氯化血红素（Hemin）组（给予血红素氧合酶-1的诱导剂）与锌原卟啉（ZnPP）组（给予血红素氧合酶-1的抑制剂）。检测各组肺组织超氧化物歧化酶（SOD）活性,血浆肿瘤坏死因子（TNF-α）含量,观察肺组织湿干重比（W／D）以及电镜下肺组织超微结构变化。结果Hemin组肺湿／干重比（5．92±0．66）低于I／R组（7．55±0．66）（P〈0．01）,SOD活性（9．2±0．5）高于I／R组（2．8±0．4）（P〈0．01）,TNF-α含量（60．37±8．25）低于I／R组（452．26±22．59）（P〈0．01）,电镜下肺组织超微结构损伤改变明显减轻;而给予ZnPP（ZnPP组）后使上述改变发生逆转。结论血红素氧合酶-1的诱导可有效保护肺缺血再灌注损伤。     

血红素加氧酶-1重组乳酸乳球菌灌胃对内毒素诱导大鼠急性肺损伤的作用

目的:利用基因工程原理合成携带血红素加氧酶-1(HO-1)基因的乳酸乳球菌,给正常大鼠灌胃后,观察其对内毒素诱导大鼠急性肺损伤的保护效应。方法:随机将30只健康清洁级SD大鼠分为对照组(LPS组,n=10)、携带HO-1的乳酸乳球菌灌胃组(HO组,n=10,LPS模型建立前24 h灌胃)、拮抗剂组[锌原卟啉(ZnPP)组,n=10,HO灌胃24 h后,LPS模型建立前1 h腹腔注射ZnPP 10μmol/kg];LPS模型建立后4 h取材,比较各组动物支气管灌洗液(BALF)中髓过氧化物酶(MPO)活性、中性粒细胞(PMN)计数、肺组织湿干重比(W/D)、肺组织MPO活性,并在光镜下观察肺组织病理学改变。结果:与LPS组比较,HO组BALF中MPO、PMN计数和肺组织W/D均降低(P<0.05),肺组织病理学损伤减轻;与HO组比较,ZnPP组BALF中MPO、PMN计数和肺组织W/D均升高(P<0.05),肺组织病理学损伤加重;ZnPP组与LPS组比较差异无统计学意义(P>0.05)。结论:预先给大鼠用携带HO-1基因的乳酸乳球菌灌胃,可对内毒素诱导急性肺损伤大鼠产生一定的保护作用。     

血红素氧合酶-1对大鼠主动脉平滑肌细胞增殖的影响

目的探讨血红素氧合酶-1(HO-1)蛋白表达对大鼠主动脉平滑肌细胞(RASMC)增殖的影响。方法大鼠主动脉平滑肌细胞株经复苏、传代培养后用于实验,设置空白对照组、HO-1诱导组、HO-1抑制组,后两组分别加用血晶素、锌原卟啉Ⅸ与细胞共同孵育,用Western blot法检测HO-1表达量,并检测HO-1活力;用MTT法检测RASMC增殖能力。同时,还观察了血晶素、锌原卟啉Ⅸ的细胞毒性作用。结果上调HO-1蛋白表达及升高HO-1活力能显著抑制血清刺激的RASMC增殖,反之,抑制HO-1蛋白表达及其活力则增强血清刺激的RASMC增殖。实验浓度的血晶素、锌原卟啉Ⅸ无明显细胞毒性作用。结论 HO-1蛋白高表达能有效抑制RASMC增殖。     

Effects of nitric oxide and carbon monoxide on CRH secretion from cultured placental trophoblasts

Humanplacentasecreteslargeamountsofhypothalamichormone,corticotropin--releasinghormone(CRH))intobothmaternalandfetalcirculationduringpregnancy.MaternalplasmaCRHrisesfrommidgestationtotermandpeakatlaborinpregantwomen.TheplacentalsyncytiotrophoblastcontainingbothCRHpeptideanditsgeneislikelytobethemajorsourceofthiscirculatingCRH.PlacentalCRHhasrecentlybeenlinkedtoplacentalclockdetermininggestationallengthandtobeatriggerofhumanlabor[lj.Inaddition,abnormallyelevatedCRHconcentrationsinmatern…     

RDP1258免疫调节功能在大鼠体内实验研究

目的观察一种新型HLA衍生肽(RDP1258)的体内免疫抑制功能并探讨其机制.方法人工固相合成HLA衍生肽(RDP1258),以3H-TdR法观察其在体内对大鼠脾细胞增殖反应的影响;与HO-1酶活性激动剂HEMIN及拮抗剂ZNPP相对比,采用酶化学法及免疫组化方法观察其对体内脾细胞血红素氧合酶-1(heme oxygenase-1,HO-1)活性的影响.结果RDP1258体内应用可显著抑制淋巴细胞转化及MLR的增殖反应;该肽能够明显提高体内HO-1活性,并增强HO-1的表达.结论RDP1258体内应用能够显著抑制大鼠脾细胞由丝裂原或同种抗原引起的增殖反应,这种作用可能是通过影响HO-1活性而达到的.     

Protective effects of hemin pretreatment combined with ulinastatin on septic shock in rats

Background Urinary trypsin inhibitor inhibits the enhanced production of pro-inflammatory molecules. Hemeoxygenase-1 induction protects against ischemia/repeffusion injury, oxidative stress, inflammation, transplant rejection, apoptosis, and other conditions. However, it is unknown if a combined hemin and ulinastatin pretreatment could result in protective effects for septic shock. In this study, we investigated the role of hemin pretreatment combined with ulinastatin on septic shock in rats. Methods Eighty healthy, male Sprague-Dawley rats were randomly divided into four groups： group S, group H, group U and group HU. Groups S and U received 1 ml normal saline intraperitoneally, while groups H and HU both received 1 ml （100 mg/kg） hemin. Twenty-four hours later, 0.5 ml （10 mg/kg） E. coil lipopolysaccharide was injected intravenously to replicate the experimental model of septic shock. After an initial 25% decrease in the mean arterial pressure, corresponding to time point 0, groups HU and U received 0.5 ml 10 000 U/kg ulinastatin intravenously, and the others received 0.5 ml normal saline. Results The number of deaths in groups H and U was lower than that in the group S （P〈0.05）, and was higher than that in group HU （all P〈0.05） respectively. The mean arterial pressure （MAP） in the group S was significantly greater than that in group H （P〈0.05）, and was lower than that in group HU and group U （P〈0.05）. The plasma levels of alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, creatinine （Cr） and blood urea nitrogen （BUN）, the malondial- dehyde （MDA） of liver, kidney and lung, and the lung Evans blue （EB） contents in groups H and U, were greater than that in group HU （all P〈0.05）, and were lower than that in group S （all P〈0.05）. In contrast, the plasma levels of CO in groups H and HU were higher than that in groups S and U （all P〈0.05）, and SOD of liver, kidney and lung in groups H and U were higher than that in group S,     

The Role of Endogenous Carbon Monoxide in the Hypoxic Vascular Remodeling of Rat Model of Hypoxic Pulmonary Hypertension

Itisknownthatpulmonaryvascularremodelingisthekeymechanisminthedevelopmentofchronicpulmonaryhypertension ,whichischaracterizedbythethicknessofthemediacausedbytheproliferationofsmoothmusclecellsandthemusculizationoftheintra acinarpulmonaryarteries[1] .Hemeoxygenase(HO)catalyzesthebreakdownofhemeintocarbonmonoxide (CO ) ,biliverdinandironinmammals .TherearetwoisoformsofHO ,HO 1andHO 2 [2 ] .HO 1istheinducibleisoformwhichcanbeinducedbyhyoxia ,shockandotherstresssettingsand pro duceCO .Itwasr…     

Distribution of endotoxins in tissues and circulation and its effects following hemorrhagic shock

OBJECTIVE: To systemically investigate 1) distribution of endogenous endotoxin (ET) in tissues and circulation; 2) its relationship with shock duration and organ damage; and 3) its possible mechanism after hemorrhagic shock. METHODS: To further elucidate the intrinsic relationship between endogenous endotoxin translocation and hemorrhagic shock, the present study systematically investigated the distribution of endogenous ET into the liver, lungs, kidneys and circulation, and the relationship between ET levels and the corresponding organ dysfunction with limulus amebocyte lysate (LAL) chromogenic assay following hemorrhagic shock in rats. RESULTS: It was found that ET levels in hepatic homogenate markedly increased (P = 0.09) 1.5 hours following shock compared with that in the sham group. After resuscitation, ET levels in hepatic, pulmonary and renal tissues were all significantly elevated. The levels kept increasing with the prolonged experimental time, and reached as high as 3.88 +/- 0.95 EU (endotoxin unit)/g in the livers, 2.53 +/- 1.46 EU/g in the lungs and 2.51 +/- 0.89 EU/g in the kidneys 12 hours after shock. ET levels in plasma reached a peak of 1.13 +/- 0.42 EU/ml at 1 hour following resuscitation, then rapidly decreased to the sham levels 3 hours following resuscitation. There was a close relationship between endotoxin translocation and shock duration. Correlation analysis further indicated that the changes in glutamic-pyruvic transaminase (GPT), blood urea nitrogen (BUN) in plasma and angiotensin I-converting exzyme (ACE) in pulmonary homogenate were significantly and positively correlated with the ET levels in the liver, kidneys and lungs after hemorrhagic shock. CONCLUSIONS: Hemorrhagic shock can induce obvious endogenous ET translocation, which is closely related to the shock duration. Although only transient endotoxemia occurs after hemorrhagic shock, ET can massively accumulate in tissues (liver, lungs and kidneys), and may play an important role in the development of shock.     

Existence of Heme Oxygenase-carbon Monoxide-cyclic Guanosine Monophosphate Pathway in Human Trabecular Meshwork Cells In Vitro

To confirm the existence of heme oxygenase (HO)-carbon monoxide (CO)- cyclic guanosine monophosphate (cGMP) pathway in the cultured human trabecular meshwork cells (HT-MCs) in vitro, and to evaluate the inductive role of heroin on this pathway, HTMCs of the third to fourth generation were cultured in vitro. Reverse transcripase-polymerase chain reaction (RT-PCR) was employed for detection of HO-1 and HO-2 mRNA. Immunohistochemical staining was used to detect HO-1 and HO-2 proteins. Hemin was added into the culture solution. The HO-1 mRNA levels were quantified by RT-PCR. The relative amount of carbon monoxide released into the media was measured with the quantifying carbon monoxide hemoglobin (HbCO) by spectrophotometry.Radioimmunoassay was used to determine changes of cGMP in HTMCs. The results showed that cultured cells had the specific characteristics of HTMCs. Both HO-1 and HO-2 genes were expressed in HTMCs, as well as HO-1 and HO-2 proteins in HTMCs. Hemin induced HO-1 mRNA,HbCO and cGMP in a dose-dependent manner. In conclusion, HO-CO-cGMP pathway exists in the cultured HTMCs and can be induced by hemin. Pharmacological stimulation of HO-CO-cGMP pathway may constitute a novel therapeutic approach to rescuing glaucoma.     

氯高铁血红素对妊娠期高血压大鼠的治疗及机制

目的初步探讨血红素氧合酶诱导剂氯高铁血红素（Hemin）对妊娠期高血压（HDCP）大鼠的治疗作用及可能调控机制。
方法将18只受孕SD大鼠于妊娠第12天随机分为3组（6只/组）：HDCP模型组、Hemin干预组、正常妊娠组。HDCP模型组和
Hemin干预组于妊娠第14天起连续7 d予亚硝基左旋精氨酸甲酯（80 mg/kg）灌胃建立HDCP模型,正常妊娠组予等量生理盐水
灌胃处理,Hemin干预组于妊娠第16天起每日下午腹腔注射Hemin（30 mg/kg）。用分光光度法测定各组胎盘组织血红素氧合
酶（HO）的活性和碳氧血红蛋白（COHb）水平,ELSIA测定各组胎盘组织匀浆上清液可溶性血管内皮生长因子受体-1（sFIt-1）、
血管内皮生长因子（VEGF）水平。结果妊娠第20天,HDCP模型组孕鼠血压和24 h尿蛋白明显高于正常妊娠组和Hemin干预
组（P<0.05）,而HO活性和COHb含量明显低于正常妊娠组和Hemin干预组（P<0.05）,Hemin干预组血压及24 h尿蛋白高于正
常组（P<0.05）,而HO活性和COHb含量较正常组低（P<0.05）;HDCP模型组孕鼠胎盘组织sFIt-1水平明显高于正常妊娠组和
Hemin干预组（P<0.05）,而胎盘组织中VEGF水平明显低于正常妊娠组和Hemin干预组（P<0.05）,Hemin干预组孕鼠胎盘组织
sFIt-1水平高于正常组水平（P<0.05）,而VEGF水平低于正常组水平（P<0.05）。结论Hemin能够降低妊娠期高血压孕鼠的血
压及尿蛋白,其可能机制是通过上调胎盘组织中HO的活性,增加代谢产物CO,降低胎盘组织中sFIt-1,并升高VEGF水平来发
挥调控作用的。
     

ROLE OF ENDOGENOUS CARBON MONOXIDE IN NEOINTIMAL FORMATION INDUCED BY BALLOON-INJURY IN RAT AORTA

ＩＮＴＲＯＤＵＣＴＩＯＮＰｅｒｃｕｔａｎｅｏｕｓｔｒａｎｓｌｕｍｉｎａｌａｎｇｉｏｐｌａｓｔｙｉｓｎｏｗａｗｅｌ－ｅｓｔａｂｌｉｓｈｅｄａｎｄｆｒｅｑｕｅｎｔｌｙｐｅｒｆｏｒｍｅｄｐｒｏｃｅｄｕｒｅｔｈａｔｉｓｃｏｍｐｌｉｃａｔｅｄｂｙｒｅｓｔｅｎｏ...     

低氧肺动脉高压时血红素氧合酶基因表达状况的研究

目的 探讨血红素氧合酶(heme oxygenase,HO)基因在低氧肺动脉高压大鼠肺动脉组织中的表达及一氧化碳(carbon monoxide,CO)对其的影响.方法 60只Wistar大鼠随机分为5组:常氧组;低氧肺动脉高压组;血晶素组;锡原卟啉组;低浓度CO组(n=12).采用紫外分光光度计、逆转录-聚合酶链反应、免疫组织化学染色和原位杂交进行检测.结果 ①HO-1活性:低氧组、血晶素组、低浓度CO组肺动脉组织HO-1活性以胆红素生成量计算,均升高,其中血晶素组最高,与正常对照组比较,差异有显著性(P<0.01).②逆转录-聚合酶链反应:各组大鼠肺动脉HO-2 mRNA表达没有明显变化,均保持稳定.缺氧组、血晶素组、锡原卟啉组和低浓CO组HO-1 mRNA均明显高于正常对照组,以低浓度CO组升高最明显(P<0.01).血晶素组和低浓度CO组均显著高于缺氧组(P<0.01),而锡原卟啉组低于缺氧组.③免疫组织化学染色:低氧组肺动脉内膜、中膜的HO-1表达均明显升高,血晶素组和低浓度CO组更高,锡原卟啉组和常氧组均有很微弱表达.④原位杂交:低氧组肺动脉3层均加深2～3级,低浓度CO组肺动脉外、中、内膜细胞质均明显加深4级.处理前后HO-2的染色变化不大.结论 低氧肺动脉高压时,肺动脉组织HO-1基因的表达升高,可能在肺动脉高压的发生和发展中起一定作用. mRNA均明显高于正常对照组,以低浓度CO组升高最明显(P<0.01).血晶素组和低浓度CO组均显著高于缺氧组(P<0.01),而锡原卟啉组低于缺氧组.③免疫组织化学染色:低氧组肺动脉内膜、中膜的HO-1表达均明显升高,血晶素组和低浓度CO组更高,锡原卟啉组和常氧组均有很微弱表达.④原位杂交:低氧组肺动脉3层均加深2～3级,低浓度CO组肺动脉外、中、内膜细胞质 明显加深4级.处理前后HO-2的染色变化不大.结论 低氧肺动脉高压时,肺动脉组织HO-1基因的表达升高,可能在肺动脉高压的发生和发展中起一定作用. mRNA均明显高于正常对照组,以低浓度CO组升高最明显(P<0.01).血晶素组和低浓度CO组均显著高于缺氧组(P<0.01),而锡原卟啉组低于缺氧组.③免疫组织化学染色:低氧组肺动脉内膜、中膜的HO-1表达均明显升高,血晶素组和低浓度CO组更高,锡原卟啉组和常氧组均有很微弱表达.④原位杂交:低氧组肺动脉3层均加     

CI-IANGES IN THE PLASMA LEVELS OF PGE, PGF2a AND 6-Keto-PGFla IN CANINE ENDOTOXIC SHOCK

The plasma levels of PGE, PGF2a and 6-keto PGFla in the canine model of endotoxic shock were determined with radioimmunoassay. Following cndotoxin injection, the PGF2a levels were rapidly increased to peak at 5 minutes. There was a negative correlation between the PGE level and the change in total systemic peripheral resistance at early stage of shock. The administration of anisodamine 2 hours after endotoxin injection showed no effect on the changes of PGE and PGF2a levels in the shocked dogs. The plasma levels of PGE and PGF2a in the shocked children with fulminating epidemic menin gococcal meningitis were also markedly elevated dur- ing shock but fell within normal range at convales- sence. After the dogs were given endotoxin the plasma level of 6-keto-PGFla increased slowly during the first hour, reached a peak at 2 hours and re mained high for 12 hours. There was a negative correlation between the 6keto-PGFla level and the blood pressure. The plasma 6keto PGFla level was decreased and the blood pressure improved corres- pondingly with a negative linear correlation as a result of administration of anisodamine 5-10 minutes after endotoxin injection. These results suggested that PGE and PGI2, as one of the humoral factors, might participate at least partially in the endotoxin induced hypotension, and that the inhibition of PGI2 synthesis was considered contributable to certain degree to the antishock effect of anisodamine.     

Existence of heme oxygenase-carbon monoxide-cyclic guanosine monophosphate pathway in human trabecular meshwork cells in vitro

Summary To confirm the existence of heme oxygenase (HO)-carbon monoxide (CO)- cyclic guanosine monophosphate (cGMP) pathway in the cultured human trabecular meshwork cells (HTMCs)in vitro, and to evaluate the inductive role of hemin on his pathway, HTMCs of the third to fourth generation were culturedin vitro. Reverse transcipase-polymerase chain reaction (RT-PCR) was employed for detection of HO-1 and HO-2 mRNA. Immunohistochemical staining was used to detect HO-1 and HO-2 proteins. Hemin was added into the culture solution. The HO-1 mRNA levels were quantified by RT-PCR. The relative amount of carbon monoxide released into the media was measured with the quantifying carbon monoxide hemoglobin (HbCO) by spectrophotometry. Radioimmunoassay was used to determine changes of cGMP in HTMCs. The results showed that cultured cells had the specific characteristics of HTMCs. Both HO-1 and HO-2 genes were expressed in HTMCs, as well as HO-1 and HO-2 proteins in HTMCs. Hemin induced HO-1 mRNA, HbCO and cGMP in a dose-dependent manner. In conclusion, HO-CO-cGMP pathway exists in the cultured HTMCs and can be induced by hemin. Pharmacological stimulation of HO-CO-cGMP pathway may constitute a novel therapeutic approach to rescuing glaucoma. LI Tao, male, born in 1976, Doctor in Charge