葛根素联合小檗碱干预非酒精性脂肪性肝炎两种动物模型的病理学研究

目的:从病理学的角度探讨葛根素及小檗碱对非酒精性脂肪性肝炎(NASH)的干预作用。方法:制备高脂饮食诱导的SD大鼠NASH模型及蛋氨酸-胆碱缺乏饮食诱导的C57BL/6小鼠NASH模型,各给药组造模并同时灌胃给药,大鼠持续8周后取材,小鼠持续2周后取材。肝组织制成石蜡切片进行HE染色,制成冰冻切片进行油红O染色,经光镜观察摄片后,采用NAFLD活动度积分对各组进行NASH评估。结果:HE及油红O检测提示葛根素联合小檗碱可减轻两种NASH动物模型肝脏的脂肪变性、抑制肝细胞空泡化的发生,减少肝小叶内炎性病灶的数量。给予葛根素联合小檗碱的SD大鼠NAS总分为2.60±0.52(3),给予葛根素联合小檗碱的C57BL/6小鼠NAS总分为2.80±0.79(3),均已排除NASH。结论:葛根素联合小檗碱可显著抑制NASH相关病理变化的发生发展,对NASH具有一定的干预作用。     

小檗碱对2型糖尿病大鼠肾组织PPARα/δ/γ表达的影响

目的:观察2型糖尿痛大鼠肾组织PPARα/δ/γ蛋白的表达及小檗碱对它们的影响.方法:小剂量注射链脲菌素(35 mg·kg-1,ip)加高糖高脂饲料饲养16周建立2型糖尿病大鼠模型,随后16周每天分别给予低中高剂量小檗碱75、150、300mg·kg-1、非诺贝特100mg·kg1 和罗格列酮4mg·kg-1,处死大鼠后用免疫组化技术检测肾脏组织中PPARα/δ/γ的表达.结果:糖尿病大鼠肾脏中PPARα和PPARδ蛋白表较正常对照大鼠明显降低(P＜0.01),PPARγ表达则较正常对照大鼠明显升高(P＜0.01).中高剂量小檗碱和非诺贝特都能促进糖尿病大鼠肾组织中PPARα和PPARδ的表达(P＜0.01),中高剂量小檗碱和罗格列酮能明显降低PPARγ表达(P＜0.01).结论:糖尿病大鼠肾脏组织中PPARα/δ/γ的表达失常,小檗碱能恢复其表达至接近正常大鼠水平.     

替米沙坦对非酒精性脂肪肝大鼠肝组织PPARs及脂联素受体2表达的影响

目的探讨替米沙坦对非酒精性脂肪肝大鼠肝组织PPARs及脂联素受体2表达的影响。方法 40只雄性SD大鼠随机分为正常对照组(NC,n=15)、高脂对照组(FC,n=15)、高脂+替米沙坦干预组(FT,n=10)。NC组给予普通饲料,FC和FT组予高脂饲料喂养。12周末时随机取NC组和FC组各5只做正葡萄糖高胰岛素嵌夹实验和肝组织HE染色,确定造模成功后,FT组给予替米沙坦5 mg/(kg·d)灌胃,NC和FC组以等容量生理盐水灌胃,共4周。16周时应用高胰岛素正葡萄糖嵌夹实验技术稳态葡萄糖输注速率测定胰岛素敏感性,检测血清转氨酶、血脂及空腹血糖水平;应用逆转录聚合酶链反应法测定肝组织中过氧化物本酶体增殖活化受体(PPARs)、脂联素受体2(AdipoR2)和血管紧张素II 1型受体(AT1R)的表达。结果与NC组相比,FC组肝组织PPARα、PPARγ、AdipoR2 mRNA表达显著下降(P0.01),AT1R mRNA表达较NC组升高(P0.01);FT组PPARα、PPARγ、AdipoR2 mRNA表达较FC组升高(P0.01);FT组血清转氨酶、血脂及空腹血糖水平较FC组改善。结论替米沙坦能降低NASH大鼠的体重和肝指数,调节糖脂代谢并改善胰岛素抵抗状态,对NASH大鼠肝脏具有保护作用。     

替米沙坦抑制SOCS-3/SREBP-1c通路改善非酒精性脂肪性肝炎模型大鼠的胰岛素抵抗

目的探讨替米沙坦对高脂饮食诱导的非酒精性脂肪性肝炎大鼠肝组织SOCS-3通路的抑制作用及对胰岛素抵抗的干预作用。方法 70只雄性SD大鼠随机分为A(20只,正常对照)、B(30只,模型对照)和C组(20只,实验干预)。A组大鼠喂以普通饲料,B和C组喂以高脂饲料;12周末随机处理B组10只,行正葡萄糖高胰岛素钳夹试验,证实IR-NASH造模成功(100%)后,B、C两组继续高脂喂养,并予C组大鼠替米沙坦每日5 mg/kg灌胃,16周末全部大鼠测血清IL-6、TG、TC、ALT、AST、空腹血糖(FBG)和血清胰岛素(FBI),并计算胰岛素抵抗指数;行正葡萄糖高胰岛素钳夹试验,肝组织HE肝脏病理学检查,半定量RT-PCR法检测肝组织SOCS-3和SREBP-1c mRNA表达水平。结果高脂饮食12周大鼠进展为NASH。16周末,B组大鼠肝湿重显著高于A组,C则明显低于B组;B组出现血脂异常和IR,血清IL-6、肝脏SOCS-3 mRNA和SREBP-1c mRNA表达水平明显上调(与A组比较P0.01),三者分别与稳态葡萄糖输注率(VGIR60-120)显著负相关(r=0.9248,P0.0001;r=0.9011,P0.0001;r=0.9739,P0.0001)。替米沙坦干预后,肝功能和血脂异常明显改善,NASH病理明显好转,SOCS-3 mRNA和SREBP-1c mRNA较B组显著下调(P0.01),同时VGIR60-120明显增高(r=0.9532,P0.0001;r=0.9687,P0.0001),表明IR明显改善;而此时IL-6仍高水平,与VGIR60-120、SOCS-3、SREBP-1c失去相关关系(r=0.0071,P=0.7238;r=0.0019,P=0.8560;r=0.0002,P=0.9586),而SOCS-3 mRNA和SREBP-1c mRNA仍显著相关(r=0.9439,P0.0001)。结论替米沙坦干预NASH大鼠可显著减改善肝功能和IR,其机制并非抑制炎症因子IL-6,而是下调肝脏SOCS-3、SREBP-1c的表达,从而改善糖脂代谢和NASH。     

益生菌对高脂饮食诱导的大鼠胰岛素抵抗的影响

目的 观察益生菌对高脂饲料喂养的SD大鼠胰岛素抵抗的影响.方法 30只雄性健康SD大鼠正常喂养1周后,随机分为正常对照组、高脂模型组、益生菌干预组[即在高脂饲料喂养的基础上给予培菲康210 mg/(只·d)灌胃].14周末,处死所有大鼠,测量大鼠体重,检测血清及肝匀浆液中脂质和葡萄糖的变化,评价胰岛素抵抗程度,并检测血浆内毒素水平.结果 (1)与对照组比较,模型组大鼠肝指数明显升高(P＜0.05);益生菌治疗后肝指数无明显降低(P＞0.05).(2)与对照组比较,模型组存在脂质代谢紊乱(P＜0.05),益生菌治疗后脂代谢紊乱明显改善(P＜0.05).(3)与对照组比较,模型组胰岛素抵抗指数明显升高(P＜0.05),胰岛素敏感指数明显降低(P＜0.05),存在胰岛素抵抗,益生菌治疗后胰岛素抵抗改善(P＜0.05).(4)与对照组比较,模型组血浆内毒素水平明显升高(P＜0.05),存在内毒素血症,益生菌治疗后内毒素血症减轻(P＜0.05).结论 益生菌可减轻内毒素血症,改善高脂饮食诱导的胰岛素抵抗.     

罗格列酮对果糖饲养SD大鼠肝肾功能、血脂、血常规的影响

目的:了解罗格列酮(Rosiglitazone)处理果糖饲养的SD大鼠后对肝、肾功能,血常规的影响。方法:将24只成年健康SD大鼠随机分为A、B两组。A组持续喂高果糖饲料1月后再随机分为:①高果糖饲养组;②果糖饲养同时用罗格列酮处理组。B组喂标准饲料1月后随机分为:①对照组;②罗格列酮处理组。采用氧化酶法、放免法等技术方法测定大鼠的空腹血糖、血脂、胰岛素水平,肝功能,肾功能,血常规等指标。结果:与对照组相比:果糖饲养组大鼠直接胆红素、总胆红素、间接胆红素、血糖、胰岛素、总胆固醇、甘油三酯等指标均升高;而总蛋白、钾、钠、氯、胰岛素敏感指数等指标均下降,差异均具有统计学意义(P＜0．05)。而罗格列酮处理组中总胆红素、间接胆红素、尿酸和尿素/肌酐等指标均升高;而总蛋白、球蛋白、钾、钠、氨水平、甘油三酯、血常规细胞数、血红蛋白均下降,差异具有统计学意义(P＜0．05)。与果糖饲养组相比,果糖饲养罗格列酮处理组的总胆红素、直接胆红素、谷草转氨酶、间接胆红素、谷丙转氨酶、总胆固醇均升高;而胰岛素、甘油三酯、钙离子水平均下降差异均具有统计学意义,且前面三个指标的差异更明显(P＜0．05)。结论:罗格列酮在治疗过程中虽改善了果糖饲养SD大鼠所引起的胰岛素抵抗,但会加重肝肾功能障碍;对机体有一定的毒副作用。     

明日叶查尔酮对2型糖尿病大鼠红细胞胰岛素受体亲和力的影响

目的:研究明日叶查尔酮对2型糖尿病大鼠红细胞胰岛素受体亲和力的影响.方法:将高脂喂养加链脲佐菌素注射诱发的2型糖尿病大鼠随机分为4组,每组10只.糖尿病对照组和高、中、低剂量组喂饲高脂饲料分别经口灌胃明日叶查尔酮0、30、10、5mg (kg·bw)-1,正常对照组为正常大鼠喂饲普通饲料,连续4周.测定空腹血糖、血清胰岛素与MDA、红细胞胰岛素受体结合常数与结合容量等指标.结果:高剂量组的高亲和力与低亲和力胰岛素受体结合常数高于糖尿病对照组,血糖、胰岛素和MDA含量则降低,差异均有显著性(P＜0.05).结论:明日叶查尔酮能提高2型糖尿病大鼠红细胞胰岛素受体亲和力,改善胰岛素抵抗.     

津力达对高脂诱导的胰岛素抵抗ApoE~(-/-)小鼠骨骼肌甘油三酯相关酶的影响

目的探究津力达对高脂诱导的胰岛素抵抗Apo E-/-小鼠骨骼肌甘油三酯相关基因的影响。方法将8只雄性C57BL/6J小鼠设为正常组(A组);40只雄性Apo E-/-小鼠喂养16周后分为模型组(B组)、罗格列酮组(C组)、津力达低剂量组(D组)、津力达中剂量组(E组)、津力达高剂量组(F组),开始灌胃给药,连续8周。采用酶法、BCA蛋白浓度法测定骨骼肌TG含量;OGTT评价小鼠的胰岛素抵抗程度;RT-PCR和Western blot测定小鼠骨骼肌HSL、ATGL、PPARγmRNA和蛋白表达。结果津力达能够不同程度降低小鼠的FBG、TC、TG和LDLC,升高HDL-C;下调FIns水平,提高ISI,明显改善小鼠糖耐量异常;津力达能够不同程度的上调小鼠HSL、ATGL、PPARγmRNA和蛋白表达。结论津力达能够通过调节骨骼肌甘油三酯相关酶的表达,改善高脂诱导的Apo E-/-小鼠的胰岛素抵抗。     

高脂饲喂联合链脲佐菌素诱导的Beagle犬糖尿病模型

目的应用高脂饲喂联合链脲佐菌素(STZ)构建Beagle犬T2DM模型,并观察其相关特征。方法将普通级雄性Beagle犬30只随机分为3组:对照组,高脂组,糖尿病模型组,每组10只。糖尿病模型组饲喂高脂饲料同时在饲喂2个月时注射STZ;高脂组饲喂高脂饲料;对照组饲喂普通饲料,连续饲喂5个月。定期测定动物Lee指数、空腹血糖、胰岛素、尿糖,并在3月时进行OGTT试验,试验结束后进行血脂等血液生化检测和肝、胰腺组织病理检查。结果高脂组和糖尿病模型组高脂饲养2个月后Lee指数显著增加(P0.01),并出现高胰岛素血症和胰岛素抵抗伴血脂异常;糖尿病模型组STZ注射后空腹血糖显著升高(P0.01),且持续3个月维持在高血糖水平;而高脂组的空腹血糖无明显变化(P0.05),糖尿病模型组OGTT试验3 h血糖值11.1mmol/L,且3 h未恢复,胰腺组织病理学检查出现一定程度的损伤和病变。结论高脂饲料饲喂诱导Beagle犬胰岛素抵抗和高血脂症,但未能形成高血糖状态,而高脂饲料饲喂联合注射STZ后Beagle犬在出现高血脂症的同时发生胰岛素抵抗,与人类T2DM的胰岛素抵抗伴高血糖、高胰岛素血症和高血脂等典型症状相似。     

非酒精性脂肪肝病大鼠肝脏SOCS-3 的表达与吡格列酮干预研究

目的:探讨SOCS-3在非酒精性脂肪肝病(NAFLD)发病中的作用以及吡格列酮的干预作用。方法:29只雄性SD大鼠随机分为正常对照组(8只),高脂饮食组(21只)。饲养8周后,从高质饮食组随机抽取5只大鼠证实造模成功后,将该组余下的16只大鼠继续以高脂饲料喂养,并随机分为NAFLD对照组(8只);吡格列酮干预组(8只),予以吡格列酮3mg·kg-·1d-1灌胃。16周末,处死所有大鼠,检测血糖、血胰岛素、血脂、肝脏SOCS-3 mRNA和SREBP-1c mRNA表达及肝脏病理学。结果:与正常对照组相比,NAFLD组血糖、血胰岛素、血脂、肝脏脂肪变水平及肝组织SOCS-3 mRNA、SREBP1c mRNA表达显著上调。吡格列酮干预组SOCS-3 mRNA、SREBP-1c mRNA表达较NAFLD组下调,且血糖、血胰岛素、血脂、肝脏脂肪变水平下降。SOCS-3 mRNA表达水平与胰岛素抵抗指数、SREBP-1c mRNA表达水平、肝脂肪变成显著正相关。结论:SOCS-3可能通过胰岛素抵抗及上调肝组织SREBP-1c mRNA表达参与NAFLD发病,吡格列酮能抑制肝脏SOCS-3的表达,对NAFLD有一定治疗作用。     

Recent advances in the study of Kaposi's sarcoma-associated herpesvirus replication and pathogenesis

It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.     

The structure, reproduction and taxonomy of Vidalia and Osmundaria (Rhodophyta, Rhodomelaceae)

Comprises species occurring mostly in subtidal habitats in tropical, subtropical and warm-temperate areas of the world. An analysis of the type species, V. spiralis (Sonder) Lamouroux ex J. Agardh, a species from Australia, establishes basic characters for distinguishing species in the genus. These characters are (1) branching patterns of thalli, (2) flat blades that may be spiralled on their axis, (3) width of the blade, (4) primary or secondary derivation of sterile and fertile branchlets and (5) position of sterile and fertile branchlets on the thalli. Application of the latter two characters provides an important basic method for separation of species into three major groups. Osmundaria , a genus known only in southern Australia, was studied in relation to Vidalia , and its separation from the Vidalia assemblage is not accepted. Species of Vidalia therefore are transferred to the older genus name, Osmundaria. Two new species, Osmundaria papenfussii and Osmundaria oliveae are described from Natal. Confusion in the usage of the epithet, Vidalia fimbriala Brown ex Turner has been clarified, and Vidalia gregaria Falkenberg, described as an epiphyte on Osmundaria pro/ifera Lamouroux, is revealed to be young branches of the host, Osmundaria prolifera.     

New or rare chromosome counts in Artemisia L. (Asteraceae, Anthemideae) and related genera from Kazakhstan

Fifteen chromosome counts of six Artemisia taxa and one species of each of the genera Brachanthemum, Hippolytia, Kaschgaria, Lepidolopsis and Turaniphytum are reported from Kazakhstan. Three of them are new reports, two are not consistent with previous counts and the remainder are confirmations of very scarce (one to four) earlier records. All the populations studied have the same basic chromosome number, x = 9, with ploidy levels ranging from 2x to 6x. Some correlations between ploidy level, morphological characters and distribution are noted.     

肝癌中HBV和HCV基因和抗原的分布及意义

采用原位分子杂交方法检测HCV RNA及HBV X基因;采用免疫组织化学方法研究HCV核心抗原,非结构区C33c抗原及HBxAg在肝细胞肝癌中的定位及分布.结果表明(1)HCV RNA、HBV X基因在肝细胞肝癌组织检出率分别为40%(55/136)和82%(112/136).HCV RNA定位于癌细胞的胞浆内,阳性细胞呈散在、灶状及弥漫分布三种形式;HBV X基因在肝癌细胞中的分布呈胞浆型、核型及核浆型,阳性细胞也呈上述三种分布形式;(2)HCV C33c抗原、核心抗原在肝细胞肝癌中的阳性率为81%(133/164)及86%(141/164).C33c抗原定位于癌细胞及肝细胞的胞浆内;核心抗原既定位于癌细胞核中,又可定位于胞浆中.C33c抗原阳性细胞以灶状分布为主;而核心抗原阳性细     

Selection with two alleles and complete dominance

For a plant selection model with frequency-independent viabilities, fertilities and selfing rates, it is shown that apart from global fixation, for certain parameter combinations a protected polymorphism and facultative fixation (either allele may become fixed according to initial frequencies) may both occur. Facultative fixation requires different selling rates for the dominant and recessive type. Protection of the polymorphism requires resource allocation for male and female function. In this connection the problem of purely genetically caused population extinction is discussed.
For general frequency dependence and regular segregation, the chances for establishment of a completely recessive gene are compared to those of a completely dominant gene. It is proven that the process of establishment of the recessive gene, despite a fitness advantage, may be considerably endangered by drift effects if random mating prevails. The recessive gene may reach the same effectivity in establishment as a dominant gene, only if the recessive homozygote mates exclusively with its own type during the period of establishment.