IL-37 抑制IL-18 在大鼠肺纤维化模型中的表达及意义的探讨

目的:初步研究博来霉素致肺纤维化大鼠肺组织中IL-37、IL-18 的表达水平,探讨其在PF 发生、发展中的表达及意义。方法:将45 只清洁级Wistar 大鼠按随机数字表法分为健康对照组(N 组)、博来霉素组(B 组)、地塞米松治疗组(D组),每组大鼠各15 只,B 组及D 组大鼠给予气管内注射博来霉素4 mg/ kg 制作肺纤维化模型,N 组给予相同体积生理盐水作为对照,D 组大鼠于肺纤维化造模基础上第2 天每日腹腔注射地塞米3 mg/ kg,N、B 组大鼠腹腔注射生理盐水作为对照。各组大鼠分别于造模后第7、14、28 天处死,HE 染色评价肺组织病理形态学变化,碱水解法及酶联免疫吸附法分别测定肺组织匀浆中羟脯氨酸(HYP)、IL-37 含量,RT-PCR 法测定肺组织中IL-18mRNA 表达量。结果: HE 染色显示B、D 组大鼠肺组织病理学改变由肺泡炎症逐渐发展为纤维化,B、D 组HYP 含量随时间推移逐渐升高,以第28 天为著(P<0.05);于B、D 组IL-37、IL-18mRNA 表达于第7 天升高至最高点,后逐渐降低,至第28 天均高于N 组,差异有统计学意义(P<0.05); D 组IL-37、IL-18mRNA 表达在同一时间均低于B 组(P<0.05)。结论:IL-37、IL-18 在大鼠肺纤维化发病早期起重要作用,可能参与了肺纤维化发生与发展。     

人脐带血干细胞抑制大鼠肺纤维化及肺巨噬细胞TGF-β1的表达

目的 研究人脐血间充质干细胞对博来霉素所致的大鼠肺纤维化及TGF-β1的影响.方法 取清洁级健康雄性SD大鼠60只随机分为博来霉素组(P组)、干细胞治疗组(M组)、地塞米松治疗组(D组)和阴性对照组(N组),取第2代人脐血间充质干细胞培养至第4代;P组、M组和D组分别经气管注入博来霉素制造肺纤维化模型,M组造模后立即经鼠尾静脉注入5-溴-2-脱氧尿嘧啶核苷(BrdU)标记的干细胞,D组造模后第2天开始连续7d腹腔注射地塞米松,N组经气管注入等量生理盐水,在第7、14、28天处死各组大鼠,行HE、Masson染色,免疫组织化学法观察TGF-β1表达及标记细胞情况.结果 M组第7、14、28天肺组织均可见标记的干细胞;HE及Masson染色后观察,与N组相比,P组7d时肺泡炎最明显,28 d肺纤维化程度最重,M、D组较P组轻且病理切片可见M组较D组肺泡炎及纤维化程度稍轻;肺组织中TGF-β1在P组7d时最高,M、D组明显少于P组,M组减少更明显,组间差异有统计学意义.结论 人脐血间充质干细胞可以定植于肺组织中,在肺纤维化早期通过抑制TGF-β1的表达,可能减轻肺泡炎及肺纤维化.     

细颗粒物PM2.5暴露加重博来霉素致大鼠肺纤维化

目的 探讨细颗粒物(PM2.5)暴露对博来霉素致大鼠肺纤维化的影响.方法 将大鼠分为4组:1)对照组(N组);2)PM2.5组(PM组);3)博来霉素组(BLM)(B组);4)PM2.5+博来霉素组(PM +B组);每组再分为4个亚组,均为6只.分别予以气管内滴注0.9％氯化钠注射液(1.5 mL/kg),PM2.5悬液(3.75 mg/kg),BLM悬液(3.5 mg/kg),BLM和PM2.5混悬液,于3、7、14和21 d处死大鼠,行肺组织HE染色和Masson染色,进行肺泡炎及肺纤维化评分,计数肺泡灌洗液(BALF)中白细胞及分类,ELISA法测BALF中IL-6、TNF-α和TGF-β1含量;Western blot测定Toll样受体(TLR)2和TLR4蛋白表达;测定肺组织匀浆中羟脯氨酸含量.结果 B组和PM +B组体质量较N组明显下降,PM +B组较B组体质量明显下降(P＜0.05).B组和PM +B组肺泡炎及肺纤维化评分显著高于N组和PM组.B组和PM +B组白细胞总数及中性粒细胞比例、BALF中IL-6、TNF-α和TGF-β1含量及肺组织羟脯氨酸含量均显著高于N组和PM组(P＜0.05),且PM +B组高于B组.PM组、B组、PM +B组肺组织TLR2、TLR4蛋白表达显著高于N组(P＜0.05),PM +B组显著高于B组和PM组.结论 PM2.5暴露加重博来霉素致大鼠肺纤维化,其机制可能通过上调肺组织TLR2及TLR4表达和增加IL-6、TNF-α及TGF-β1分泌.     

苦参碱对肺纤维化鼠肝细胞生长因子表达的影响

目的 探讨苦参碱对博莱霉素诱导肺纤维化大鼠肺组织肝细胞生长因子表达的影响.方法 选取SD大鼠72只,随机分为空白对照组、模型对照组、苦参碱处理组,每组各24只.各组动物于7、14、28d随机处死8只,取肺组织采用苏木精-伊红染色,Masson胶原染色及测定羟脯氨酸(HYP)浓度采评价治疗效果,用原位杂交的方法检测肝细胞生长因子(HGF)mRNA的表达,用酶联免疫吸附法(ELISA)检测HGF蛋白在大鼠肺组织的含量.结果 苦参碱组肺泡炎和肺纤维化程度及羟脯氨酸浓度低于同时期模型对照组,有统计学意义;模型组肺组织HGFm RNA表达及蛋白含量在第7d达高峰,之后下降,第14d,第28d低于正常对照组(P<0.01),苦参碱组HGFm RNA表达及蛋白含量变化趋势与模型组同,但其表达均高于同时间段模型组(P<0.05).结论 在博来霉素诱导肺纤维化形成阶段应用苦参碱干预能减轻肺纤维化的程度,其可能机制为通过促进HGF的表达而实现.     

苦参碱对肺纤维化鼠肝细胞生长因子表达的影响

目的探讨苦参碱对博莱霉素诱导肺纤维化大鼠肺组织肝细胞生长因子表达的影响。方法选取SD大鼠72只,随机分为空白对照组、模型对照组、苦参碱处理组,每组各24只。各组动物于7、14、28d随机处死8只,取肺组织采用苏木精-伊红染色,Masson胶原染色及测定羟脯氨酸（HYP）浓度来评价治疗效果,用原位杂交的方法检测肝细胞生长因子（HGF）mRNA的表达,用酶联免疫吸附法（ELISA）检测HGF蛋白在大鼠肺组织的含量。结果苦参碱组肺泡炎和肺纤维化程度及羟脯氨酸浓度低于同时期模型对照组,有统计学意义;模型组肺组织HGF mRNA表达及蛋白含量在第7d达高峰,之后下降,第14d,第28d低于正常对照组（P〈0.01）,苦参碱组HGF mRNA表达及蛋白含量变化趋势与模型组同,但其表达均高于同时间段模型组（P〈0.05）。结论在博来霉素诱导肺纤维化形成阶段应用苦参碱干预能减轻肺纤维化的程度,其可能机制为通过促进HGF的表达而实现。     

博来霉素致大鼠肺纤维化模型肺组织的动态病理变化及其发生机制

目的： 了解博来霉素（BLM）致大鼠肺纤维化模型肺组织的动态病理变化,探讨BLM致肺纤维化的作用机制。方法：60只雄性SD大鼠采用随机数字表法分为正常对照组（N组）和肺纤维化模型组（B3、B7、B14、B28、B56组）,每组10只。除N组外,其余各组采用气管内注入BLM致大鼠肺纤维化模型, 分别于3、7、14、28、56 d处死各组大鼠,右肺行苏木精-依红（HE）、Masson胶原及天狼猩红染色,测定左肺羟脯氨酸（HYP）的含量。 RT-PCR法半定量测定转化生长因子-1（TGF-β1）、基质金属蛋白酶-9（MMP-9）和基质金属蛋白酶组织抑制物-1（TIMP-1）mRNA在肺内的表达。免疫组化法观察TGF-β1、MMP-9及TIMP-1蛋白在大鼠肺组织的表达。结果：(1) 模型组大鼠肺组织HYP含量显著高于N组（P<0.05）,模型组大鼠肺组织肺泡炎症的程度也明显重于N组,B14、B28和B56组大鼠肺纤维化的程度明显重于N组,大鼠在灌注BLM后不同时点其肺组织有着不同的病理变化。 (2) TGF-β1、MMP-9及TIMP-1在正常组大鼠肺脏中即有表达,但表达较弱,灌注BLM后它们的表达均增强,不同时点它们在肺组织内的分布有不同的特点。结论：给予后不同时点大鼠肺组织有着不同的病理变化特点,TGF-β1、MMP-9和TIMP-1在BLM诱导的肺纤维化形成过程中起着重要的调节作用。     

丙戊酸钠减轻博莱霉素致大鼠肺纤维化

目的:探讨丙戊酸钠在博莱霉素诱导的肺纤维化中的作用及机制。方法:42只大鼠随机分为正常对照组、模型组和治疗组。造模采用博来霉素5 mg/kg气管内注射,自造模14 d开始分别采用生理盐水(0.5m L/d)、丙戊酸钠(300 mg·kg-1·d-1)和地塞米松(0.6 mg·kg-1·d-1)腹腔内注射治疗14 d。模型组分别在造模后14和、28 d处死。治疗组在造模后28 d处死。然后通过HE染色、Masson染色、羟脯氨酸(HYP)检测和Western blotting检测α-平滑肌肌动蛋白(α-SMA)及E-钙黏蛋白(E-cadherin)表达的变化,综合分析丙戊酸钠对肺纤维化发展的干预作用。结果:HE染色显示丙戊酸钠治疗组的肺泡结构、肺间质的形态优于生理盐水组和地塞米松治疗组。Masson染色及HYP检测用于衡量肺组织内胶原的分布及含量,可见丙戊酸钠治疗组肺组织内胶原的分布及含量均显著低于地塞米松治疗组及生理盐水组。丙戊酸钠可以降低α-SMA的表达,同时上调上皮标志性蛋白E-cadherin的表达。结论:丙戊酸钠可以通过减少胶原的表达与分布及下调间充质蛋白α-SMA,同时上调上皮蛋白E-cadherin的表达从而减轻博来霉素诱导大鼠肺纤维化。     

Th17细胞在肺纤维化小鼠中的动态变化及作用机制

目的:研究Th17细胞在博来霉素致肺纤维化小鼠中的动态变化及作用机制。方法:小鼠随机分为对照组、博来霉素组和全反式维甲酸组。博来霉素组和维甲酸组利用博来霉素建立小鼠肺纤维化模型,维甲酸组在造模第0天每只腹腔注射全反式维甲酸。评价小鼠肺组织病理形态变化;检测肺组织中羟脯氨酸含量和维甲酸相关孤儿受体(RORγt)mRNA的表达;应用流式细胞术分析脾中Th1、Th2、Th17细胞的动态变化。结果:博来霉素组和维甲酸组羟脯氨酸(HYP)含量逐渐升高,博来霉素组第7、14、28天高于对照组和维甲酸组,第28天时达最高;博来霉素组、维甲酸组在4个时间点与对照组比较,Th17、Th2细胞均明显增高,Th1细胞低于对照组,RORγt mRNA表达水平上调。其中维甲酸组Th17、Th2细胞及RORγt mRNA表达水平低于博来霉素组,Th1细胞高于博来霉素组。结论:Th17细胞可能参与特发性肺纤维化的发病机制,并通过调节Th1、Th2细胞分化来发挥作用。     

依那西普对博莱霉素所致小鼠肺纤维化的影响及其机制

目的:观察依那西普对博莱霉素诱导的小鼠肺纤维化的作用及可能机制。方法:方法将30只SPF级雄性昆明小鼠随机分为3组,即对照组、模型组、干预组,每组10只。对照组小鼠气管内灌注生理盐水,模型组小鼠气管内灌注博莱霉素5 mg/kg,干预组小鼠气管内灌注博莱霉素后,3 mg/kg依那西普腹腔注射,一周2次。于造模后28 d处死小鼠,收集肺组织,碱水解法检测羟脯氨酸含量;肺组织用4%多聚甲醛固定后,石蜡包埋切片,行HE染色及Masson染色;Western blot法检测肺组织NF-κB和磷酸化NF-κB的表达。结果:干预组小鼠肺组织羟脯氨酸含量较模型组明显下降(P0.01);干预组肺组织炎症评分较模型组明显下降(P0.01),肺纤维化评分较模型组下降(P0.01);干预组肺组织磷酸化NF-κB的表达下降(P0.01)。结论:依那西普可抑制NF-κB的磷酸化,减轻博莱霉素导致的小鼠肺部炎症程度和纤维化改变,延缓肺纤维化进展。     

甘草甜素抑制肺纤维化大鼠肺组织单核细胞趋化蛋白-1的表达

目的: 观察甘草甜素对博来霉素(BLM)诱导的大鼠肺纤维化的干预作用及可能机制。方法: 随机将大鼠分为对照组、肺纤维化模型组、甘草甜素干预组。气管内注入博莱霉素造成动物模型后,于当天开始每天给药,分别于7 、28 d处死,取肺组织,行嗜伊红染色、Masson染色；检测肺组织匀浆中羟脯氨酸(HYP) 的变化; RT-PCR法测肺组织单核细胞趋化因子-1 mRNA的表达,免疫组化测肺组织单核细胞趋化因子-1蛋白的表达。结果: 干预组肺纤维化程度轻于模型组; 肺组织匀浆羟脯氨酸(HYP)含量显著低于模型组( P<0.01) ;在模型组 MCP-1第7 d表达就明显升高，第28 d下降，但仍高于对照组，干预组与模型组有同一规律，但均减弱，第7、28 d与模型组(M组)比较，P<0.05。结论: 甘草甜素能减轻博莱霉素诱导的大鼠肺纤维化，这种作用可能部分是通过抑制MCP-1的表达而实现。     

Modes of reinforcement and gender and culture of experimenter and subject: effects of "alien" and external reinforcement for Japanese and American men and women

In this study, we examined external and "alien" reinforcement (ER and AR. respectively) as a factor in social learning, and studied the combined effects of culture and reinforcement mode. A female (Experiment 1) and a male (Experiment 2) experimenters conducted experimental sessions. Both men and women, who grew up in the same culture as the experimenter, participated and performed the experimental task. A three-way interaction effect of experimenter gender, culture, and reinforcement mode was found on task performance. And the effect was more pronounced for a Japanese experimenter. A female and a male experimenters conducted Experiments 3 and 4, respectively; however participants this time were men and women who grew up in different cultures than the experimenter. Results indicated that the pattern of the subject gender and reinforcement mode interaction effect, when the experimenter was Japanese with American subjects, was exactly opposite to that when the experimenter was American. These experiments showed that AR was as effective for social learning as ER, and that the cultural backgrounds of experimenter and subject influenced AR and ER effectiveness.     

Timing and intensity of early fevers and the development of allergies and asthma

BACKGROUND: Early childhood fevers appear to protect against later allergies and asthma. What is not known is the time in which fevers exert this effect and whether the degree of temperature increase is important. OBJECTIVE: We sought to examine the relationship between the time and degree of early fevers and later allergies and asthma. METHODS: Eight hundred thirty-five children from southeast Michigan were enrolled at birth. Clinic records from their first 2 years were abstracted for episodes of fever. At age 6 to 7 years, children underwent allergy testing. We examined fevers occurring within 6-month intervals in the first 2 years of life and outcomes at age 6 to 7 years. The primary outcome measures were allergic sensitization, asthma, asthma with allergic sensitization, and asthma without allergic sensitization. RESULTS: In the unadjusted analysis each episode of fever between 7 and 12 months of age was associated with a lower odds of allergic sensitization (odds ratio [OR], 0.71; 95% CI, 0.54-0.93) and asthma with allergic sensitization (OR, 0.43; 95% CI, 0.21-0.90) at age 6 to 7 years. Likewise, every 1 degrees C increase in the maximum temperature between 7 and 12 months was associated with a lower odds of allergic sensitization (OR, 0.77; 95% CI, 0.61-0.96) and asthma with allergic sensitization (OR, 0.62; 95% CI, 0.40-0.94). After adjusting for potential confounders, each episode of fever between 7 and 12 months was associated with a lower likelihood of asthma with allergic sensitization (adjusted OR, 0.33; 95% CI, 0.11-0.94) at age 6 to 7 years. CONCLUSIONS: Both the timing and intensity of childhood fevers appear to be important factors in the development of allergies and asthma.     

Rates of oxygen consumption and of anaerobic glycolysis in renal cortex and medulla of adult and new-born rats and guinea-pigs

1. Rates of oxygen uptake and of anaerobic glycolysis were estimated in slices from the renal cortex and medulla (a) of adult rats and guinea-pigs, (b) of new-born (1-, 5- and 21-day-old) rats and of guinea-pigs of 1, 12, 21, 24 and 120 hr age.2. In the adult rat, Q(O2) values for the cortex were 12.55 +/- 0.20 (22) and for the medulla: 8.56 +/- 0.17 (22) mul./hr.mg dry weight, while in the new-born rat (24 hr old) they were 10.99 +/- 0.46 (12) and 9.33 +/- 0.18 (9) mul./hr.mg dry weight respectively.3. Values for Q(CO2) (N2) (anaerobic glycolysis) in the 14 hr old new-born rat were in the renal cortex 9.65 +/- 0.35 (5) and in the medulla 7.39 +/- 0.43 (5) mul./hr.mg dry weight; while in the adult they were 2.25 +/- 0.08 (16) and 5.76 +/- 0.14 (16) mul./hr.mg dry weight, respectively.4. In the adult guinea-pig values for Q(CO2) (N2) were of the same order as in the adult rat, though the rate of O(2) uptake was for the cortex 8.12 +/- 0.22 (12) and for the medulla 5.02 +/- 0.23 (11) mul./hr.mg dry weight.5. Though the Q(O2) values in the renal cortex and medulla were smaller in the 1 hr old new-born guinea-pig, they were already increasing in the 12 hr old neonate.6. The results are discussed in the light of enzyme changes occurring during the process of maturation of the nephron as indicated by histochemical observations.     

Association between functional alterations of senescence and senility and disorders of gait and balance

OBJECTIVES:

Declines in cognition and mobility are frequently observed in the elderly, and it has been suggested that the appearance of gait disorders in older individuals may constitute a marker of cognitive decline that precedes significant findings in functional performance screening tests. This study sought to evaluate the relationship between functional capacities and gait and balance in an elderly community monitored by the Preventive and Integrated Care Unit of the Hospital Adventista Silvestre in Rio de Janeiro, RJ, Brazil.

METHODS:

Elderly individuals (193 females and 90 males) were submitted to a broad geriatric evaluation, which included the following tests: 1) a performance-oriented mobility assessment (POMA) to evaluate gait; 2) a mini-mental state examination (MMSE); 3) the use of Katz and Lawton scales to assess functional capacity; 4) the application of the geriatric depression scale (GDS); and 5) a mini-nutritional assessment (MNA) scale.

RESULTS:

Reductions in MMSE, Katz and Lawton scores were associated with reductions in POMA scores, and we also observed that significant reductions in POMA scores were present in persons for whom the MMSE and Katz scores did not clearly indicate cognitive dysfunction. We also demonstrated that a decline in the scores obtained with the GDS and MNA scales was associated with a decline in the POMA scores.

CONCLUSIONS:

Considering that significant alterations in the POMA scores were observed prior to the identification of significant alterations in cognitive capacity using either the MMSE or the Katz systems, a prospective study seems warranted to assess the predictive capacity of POMA scores regarding the associated decline in functional capacity.     

男性乳腺发育症临床病理分析及雌,孕激素受体检测

对１１３例男性乳腺发育症进行临床病理分析。同时检测其中３０例乳腺组织中雌激素受体和孕激素受体分布情况，结果发现两者阳性率分别为８０．０％和８３．３３％。结合文献讨论了男性乳腺发育症的发生与高血清激素浓度及乳腺组织高受体水平的关系。