二甲基亚硝胺致大鼠脂质过氧化变化与药物干预作用

目的探讨二甲基亚硝胺（ＤＭＮ）诱导大鼠肝纤维化的脂质过氧化病理机制,以及扶正化瘀方与干扰素Ｖ的干预作用。方法ＤＭＮ复制大鼠肝纤维化模型,分别以扶正化瘀方灌胃及（干扰素肌注治疗。观察项目包括肝脏病理、肝功能、肝组织羟脯氨酸（Ｈｙｐ）、丙二醛（ＭＤＡ）含量与超氧化物歧化酶（ＳＯＤ）活性。并进行Ｈｙｐ、ＭＤＡ与ＳＯＤ之间的相关分析。结果模型大鼠肝组织胶原明显增生,纤维间隔形成; ＡＬＴ水平上升;肝组织Ｈｙｐ与ＭＤＡ含量显著增加, ＳＯＤ活性显著降低,且ＳＯＤ与 ＭＤＡ、 Ｈｙｐ呈负相关（ｒ＝０．７０,－０．７３,Ｐ＜ ０．０１）,ＭＤＡ与 Ｈｙｐ呈正相关（Ｔ＝０．８８, Ｐ＜ ０．０１）。扶正化瘀方与干扰素γ均能明显减轻肝组织胶原沉积、降低ＡＬＴ水平,提高肝组织ＳＯＤ活性、降低肝组织Ｈｙｐ与ＭＤＡ含量。结论脂质过氧化是ＤＭＮ损伤大鼠并诱发肝纤维 化的主要机制之一,抗脂质过氧化是扶正化瘀方与干扰素γ抗肝纤维化的重要作用机理。     

叔丁基痉基茴香醚对小鼠醋氨酚中毒性肝损伤的操作作用

目的：采用小鼠醋氨酚中毒性肝损伤模型探讨２（３）－叔丁基－４－羟基茴香醚（ＢＨＡ）对肝脏的保护作用。方法：通过腹腔注射醋氨酚制备小鼠肝损伤模型,测定小鼠血清丙氨酸转氨酶（ＡＬＴ）活笥和肝匀浆液中的丙二醛（ＭＤＡ）含量、超氧化的岐化酶（ＳＯＤ）活性及谷胱甘肽（ＧＳＨ）含量。结果：０．２％及０．５％的ＢＨＡ都能显著对抗醋氨酚所致小鼠肝损伤的血清ＡＬＴ活性升高,肝组织ＭＤＡ含量升高、ＳＯＤ活性降低及还原     

丹酚酸A抗过氧化鼠肝损伤的作用

目的观察丹酚酸Ａ（ＳＡＡ）抗过氧化肝损伤的作用．方法采用ＣＣｌ４诱导大鼠肝损伤模型,观察ＳＡＡ对肝脏病理、血清Ａｌｂ含量与ＡＬＴ,ＡＳＴ活性,肝组织ＭＤＡ含量的影响．另以ＣＣｌ４熏蒸诱导肝细胞损伤,观察ＳＡＡ对ＡＬＴ,ＡＳＴ,ＧＳＨＰＸ的活性以及对ＭＤＡ,ＧＳＨ含量的变化．结果ＳＡＡ能减轻模型鼠肝脏病理变化,降低ＡＬＴ,ＡＳＴ活性与ＭＤＡ含量;降低损伤肝细胞ＡＬＴ,ＡＳＴ,ＳＯＤ,ＧＳＨＰＸ活性与ＭＤＡ含量,增高ＧＳＨ含量．结论ＳＡＡ具有良好的抗过氧化肝损伤作用．     

一氧化氮和自由基对大鼠急性肝损伤的作用

目的用硫代乙酰胺（ＴＡＡ）诱发大鼠急性肝损伤,观察肝损伤过程中一氧化氮与自由基的变化．方法实验Ⅰ：大鼠２４只分为４组,一组为正常组,其余３组为损伤组．ＴＡＡ６００ｍｇ／ｋｇｓｃ２４,４８,７２ｈ测定内毒素及ＮＯ３－／ＮＯ２－,ＡＬＴ,ＡＳＴ含量．取肝组织匀浆,测定蛋白含量．脂质过氧化物歧化酶（ＳＯＤ）及谷胱甘肽过氧化物酶（ＧＳＨＰＸ）活性,并观察肝组织学变化．实验Ⅱ：大鼠３２只分为４组,Ａ组为正常组,Ｂ,Ｃ,Ｄ组ＴＡＡ６００ｍｇ／ｋｇｓｃ;同时给予Ｂ组生理盐水０４ｍＬ／ｋｇ,Ｃ组７５％ＬＡｒｇ３００ｍｇ／ｋｇ,Ｄ组２５％ＬＮＮＡ１０ｍｇ／ｋｇ．２４ｈ后重复注射１次．２４ｈ后按实验Ⅰ取血、肝组织,测定有关指标．结果大鼠注射ＬＡｒｇ后,ＮＯ的合成增多,转氨酶及肝组织损伤程度明显降低,注射ＬＮＮＡ组大鼠肝损伤程度加重,肝组织自由基的测定表明,抑制肝损伤大鼠ＮＯ合成,肝组织ＬＰＯ含量增高而ＳＯＤ,ＧＳＰＨＸ活性降低,ＳＯＤ,ＧＳＨＰＸ协同作用可清除体内自由基．结论抑制ＮＯ的生物合成,自由基水平增高,从而加重了肝损伤     

扶正化瘀方对DMN诱导肝纤维化大鼠肝脏MMP-2活性的影响

探讨扶正化瘀方对二甲基亚硝胺 (ＤＭＮ)诱发的肝纤维化大鼠肝脏Ⅳ型胶原含量、Ⅳ型胶原酶 (ＭＭＰ 2 )活性及基质金属蛋白酶抑制物 2 (ＴＩＭＰ 2 )含量表达的影响。采用ＤＭＮ诱导的大鼠肝纤维化模型 ,设正常组、模型组和扶正化瘀方治疗组 ,分别用生化方法测定其肝组织Ｈｙｐ含量、血清ＡＬＴ活性和Ａｌｂ含量 ;Ｅｎｖｉｓｉｏｎ两步法 (免疫组化 )测定肝组织Ⅳ型胶原含量和ＴＩＭＰ 2含量 ;酶图法测定肝组织ＭＭＰ 2活性。结果表明 :①扶正化瘀方能显著降低模型大鼠肝组织Ｈｙｐ及血清ＡＬＴ ,显著升高血清Ａｌｂ ;②扶正化瘀方能够明显降低ＤＭＮ诱发的肝纤维化鼠肝脏的Ⅳ型胶原和ＴＩＭＰ 2 ,显著升高其ＭＭＰ 2活性。扶正化瘀方能够明显改善ＤＭＮ诱发的肝纤维化鼠的病理改变和生化指标 ;能够明显升高ＤＭＮ诱发的肝纤维化大鼠肝脏ＭＭＰ 2活性 ,并显著降低其ＴＩＭＰ 2的表达 ,促进过多的Ⅳ型胶原的分解 ,加速肝窦毛细血管化的恢复。扶正化瘀方对DMN诱导肝纤维化大鼠肝脏MMP-2活性的影响@徐光福!200032$上海中医药大学肝病研究所 @陆雄!200032$上海中医药大学肝病研究所 @刘成海!20003...     

咖啡因血浆半衰期定量肝功能

将四氯化碳（ＣＣｌ４）注入ＳＤ雄性鼠腹腔造成急性肝损伤模型，分别于２４ｈ、４８ｈ做血浆咖啡因清除试验，同时检测鼠血ＡＬＴ水平、肝组织学改变及肝组织含水量。结果表明：用ＣＣｌ４后２４ｈ，肝组织有片状坏死，肝细胞广泛变性，肝组织含水量显著增加，血浆ＡＬＴ显著升高，咖啡因血浆半衰期（ＣＡｔｌ／２）显著延长；４８ｈ后，以上指标仍校对照组有显著差异。总体分析显示：ＣＡｔｌ／２与ＡＬＴ、肝组织含水量变化均呈平行关系，且ｃＡｔｌ／２与ＡＬＴ（ｒ＝０．７５３，Ｐ＜０．０１）、肝组织含水量（ｒ＝０．７０１，Ｐ＜０．００２）均显著正相关，说明：①ＣＡｔｌ／２可作为急性肝损伤程度的一指标；②ＣＡｔｌ／２可定量有功能肝细胞总体。     

体外四氯化碳损伤肝细胞对肝星状细胞活化的影响及其丹酚酸A的干预效果

目的 体外观察肝细胞四氯化碳过氧化损伤后肝星状细胞（ＨＳＣ）活化的影响,并观察丹参水溶性成分丹酚酸Ａ的干预效果,以研究脂质过氧化损伤与肝纤维化的关系和丹酚酸Ａ的作用机理。方法 肝细胞分离后分组,分别添加不同浓度的丹酚酸Ａ以及对照药维生素Ｅ,同时以四氯化碳熏蒸２４ｈ并测定各组细胞上清液ＡＬＴ、ＡＳＴ活性后,换液培养２４ｈ并测定ＭＤＡ含量,再以此上清液作为“肝细胞条件培养液”作用于ＨＳＣ４８ｈ,观察Ｈ     

乙肝I号方对急性肝损伤小鼠的防护作用

目的：观察乙肝１号方治疗小鼠急性肝损伤的效果，方法：采用乙肝１号方大小剂量组灌胃，并与乙肝灵对照，治疗Ｄ－氨基半乳糖（Ｄ－Ｇａｌｎ）所致急性肝损伤小鼠，结果：治疗组小鼠肝损伤减轻，肝匀浆超氧化物歧化酶（ＳＯＤ）的含量上升，上升程度呈明显的量效关系，并优于乙肝灵治疗组，血清谷丙转氨酶（ＡＬＴ）降低，降低程度呈明显的量效关系，且优于乙肝灵治疗组，结论：乙肝１号方对小鼠急性肝损伤有明显防护作用。     

四氯化碳蒸熏法致肝细胞急性损伤时的功能变化及扶正化瘀方？…

目的：研究体外生损伤肝细胞的功能变化和扶正化瘀方药物血清的调节作用，方法：采用四氯化碳蒸熏法造成体外原代培养大鼠肝细胞急性肝损伤，检测其释放ＡＬＴ－ＡＳＴ活性，分泌白蛋白及细胞内外胶原生成率的变化，同时通过添加体内给药分离的药物血清，观察扶正化瘀方对急性损伤肝细胞病理变化的影响。结果：ＣＣｌ４体外急性损伤肝细胞后，其培养ＡＬＴ，ＡＳＴ活性及胶原生成率显著升高，增殖能力明显降低，Ａｌｂ变化不明显，扶     

急性肝坏死大鼠NO水平的动态变化和作用

目的探讨一氧化氮（ＮＯ）在急性肝坏死大鼠模型中的浓度动态变化及其可能的作用机制．方法通过用化学药物促进或抑制急性肝坏死大鼠ＮＯ的合成，检测其外周血ＮＯ及ＡＬＴ，ＡＳＴ的浓度变化，并观察肝脏的病理变化．结果①急性肝坏死大鼠血清ＮＯ浓度６，１２，２４，４８ｈ显著高于正常对照（μｍｏｌ／Ｌ，９０±１３，１３７±３１，６６±１６，４４±１０ｖｓ１６±６，分别为Ｐ＜００１，Ｐ＜００１，Ｐ＜００１，Ｐ＜００５）；ＡＬＴ，ＡＳＴ也显著升高（ＡＬＴ，Ｕ／Ｌ，６９８±１０８，２０５６±６６８，８５８±２０８，１９６±３４ｖｓ３５±１３，Ｐ＜００１；ＡＳＴ，Ｕ／Ｌ，８０１±９４，３５７５±７１４，１２７２±２４２，１７５±１２７ｖｓ６５±２２，Ｐ＜００１）；②用ＮＡＭＥ抑制ＮＯ合成，降低了急性肝坏死大鼠外周血ＮＯ浓度，却显著升高了ＡＬＴ，ＡＳＴ浓度．③急性肝坏死大鼠应用ＮＯ合成底物后，与阳性对照组相比，未见ＮＯ显著升高，ＡＬＴ，ＡＳＴ也无显著变化．结论ＮＯ对ＤＧａｌｎ／ＬＰＳ诱导的急性肝坏死大鼠肝组织具有保护作用．     

Molecular stability and function of hemoglobins Hasharon (alpha(2)47 (CD5)Asp----His beta 2) and Hasharon (alpha(2)47 (CD5)Asp----His delta 2)

The molecular stability and function of hemoglobin (Hb) Hasharon (alpha 2 H beta 2) and Hb Hasharon2 (alpha 2 H delta 2) were studied and compared to Hbs A, A2 and S. Hb Hasharon and Hb Hasharon2 had slightly lower P50 values than Hb A and Hb A2 but had normal responses to organic phosphates. The molecular stability of Hb Hasharon and Hb Hasharon2 (as measured by mechanical shaking and heat denaturation at 60 degrees C) were less than Hb A and Hb A2 but greater than Hb S in the oxy- and carbonmonoxy-forms. In the met-form, however, Hb Hasharon and Hb Hasharon2 were less stable than hemoglobins S, A and A2. The oxy-form of Hb Hasharon forms methemoglobin at a faster rate than Hb A and Hb S. The mechanical and heat stabilities and the rate of methemoglobin formation of oxy-Hb Hasharon were studied in the presence of sulfisoxazole. This drug increased the rate of methemoglobin formation, thus causing a further decrease in the stability of Hb Hasharon. The relationship between these laboratory findings and previously observed clinical findings associated with Hb Hasharon are discussed.     

Specificity and crossreactivity of idiotypes of murine antibodies induced by poly(Tyr,Glu)-poly(DLAla)-poly(Lys) and poly(Phe,Glu)-poly(DLAla)-poly(Lys)

Antibodies elicited against the two synthetic polypeptides, poly(Tyr,Glu)-poly(DLAla)-poly(Lys) [(T,G)-A-L] and poly(Phe,Glu)-poly(DLAla)-poly(Lys) [(Phe,G)-A-L], are crossreactive although the humoral responses to these immunogens are under different genetic controls. The fine specificity of the antibodies elicited by the two polypeptides was studied in the present work. Antisera against (Phe,G)-A-L bind both (125)I-labeled (T,G)-A-L and iodinated modified (Phe,G)-A-L. However, while the binding to (T,G)-A-L could be inhibited completely with the two antigens, the binding to (Phe,G)-A-L was inhibited completely with (Phe,G)-A-L and only partially with (T,G)-A-L. The binding of (125)I-labeled (T,G)-A-L to antisera against (T,G)-A-L was inhibted more efficiently by the homologous antigen than by (Phe,G)-A-L although both antigens completely inhibited the binding. (T,G)-A-L specific antibodies were purified on (T,G)-A-L immunoadsorbents from antisera of high and low responder mice to (T,G)-A-L immunized with (Phe,G)-A-L. (Phe,G)-A-L specific antibodies that did not bind (T,G)-A-L were isolated from the effluent of these columns. By use of anti-idiotypic antibodies of guinea pig against C3H.SW antibodies to (T,G)-A-L it was shown that (T,G)-A-L specific antibodies isolated from antisera against (Phe,G)-A-L of C3H.SW and C3H/DiSn mice possess part of the idiotypic determinants existing on antibodies of C3H.SW obtained by immunization with (T,G)-A-L. In contrast, antibodies to (Phe,G)-A-L that did not bind (T,G)-A-L did not share idiotypic determinants with C3H.SW antibody molecules against (T,G)-A-L. These results suggest that the B cell repertoire expressed by high and low responders to (T,G)-A-L after immunization with (Phe,G)-A-L is similar and represents only part of that of high responders immunized with (T,G)-A-L.     

Compound heterozygosity of Hb D(Iran) (beta(22) Glu-->Gln) and beta(0)-thalassemia (619 bp-deletion) in India

The present report describes the hematologic and molecular study of the second case of Hb D(Iran) associated with beta(0)-thalassemia (619 bp-deletion) found in India and the first case in which the mutations have been identified at molecular level. The patient showed hypochromic, microcytic red cell picture with reduced red cell indices. The characterization of the hemoglobinopathy was made by electrophoretic and chromatographic techniques and confirmed by sequencing of the beta-globin gene. Both the propositus and her father were found to be carriers of the gene for beta(0)-thalassemia owing to the 619 bp-deletion mutation as seen by the polymerase chain reaction (PCR). Single base substitution GAA > CAA (indicative of Hb D(Iran)) in the heterozygous form was seen in the propositus as well as the mother by sequencing.