Immunological Effect of PM2.5 on Cytokine Production in Female Wistar Rats1

Objective To investigate the immunological effect of PM2.5 on cytokine production in female Wistar rats.Methods Female Wistzr rats were given 0.3 mg,0.75 mg,2 mg,5 mg of PM2.5 per 0.5mL saline,respectively.Saline was used as the negative control.TNF-α and IL-6 levels in the branchoalveolar lavage were measured by ELISA,and mRNA expression leveIs in lung tissue were detected bv RT-PCR.Alveolar macrophages were collected for testing phogacytic function. Results Exposure to PM2.5 stimulated TNF-α production in a dose-dependent manner(P＜0.05),However,no statistically significant difference was found.No time-dependent change in TNF-α and IL-6 production Was found.TNF-α and IL-6 mRNA expressions were induced by PM2.5-exposure.The phagocytic rate(PR)was significantly decreased by PM2.5 treatment.Conclusion PM2.5 exposure increases inflammation response of the lung in a dose-dependent mauuer.Moreover,tissue injury induced by PM2.5 may be related to altered production of cytokines.PM2.5 may impair the phagocytic activity of alveolar macrophages.     

氯胺酮对内毒素诱导大鼠急性肺损伤的影响及其机制

目的探讨不同剂量氯胺酮对内毒素（LPS）诱导大鼠肺损伤的影响和作用机理。方法48只雄性Wistar大鼠随机分为4组：对照组,LPS组（5mg／kg）,低剂量氯胺酮治疗组（5mg／kg）,高剂量氯胺酮治疗组（10mg／kg）,每组12只。建立内毒素诱导的大鼠急性肺损伤模型,于注射LPS后4h处死大鼠,测肺湿／干重比,观察支气管肺泡灌洗液（BALF）中性粒细胞计数比、蛋白浓度,测肺组织中肿瘤坏死因子α（TNF-α）、白细胞介素-8（IL-8）、NO水平。RT．PCR测肺组织中．NOSmRNA表达,Western-blot测肺组织中NF-κB蛋白表达。结果LPS组大鼠肺湿／干重比、BALF中性粒细胞计数比、蛋白浓度均明显增加（P〈0．01）,肺组织中TNF-α、IL-8、NO水平显著性升高（P〈0.01）,同时肺组织中iNOSmRNA和核因子-κB（NF-κB）蛋白表达均增加。而氯胺酮治疗组的各项指标均较LPS组减轻,大剂量组作用更明显。结论氯胺酮通过抑制NF-κB表达,减少炎症性细胞因子的产生,从而对内毒素（LPS）诱导的大鼠肺损伤有一定保护作用。     

白屈菜赤碱对大鼠肺组织的长期毒性作用及其对肺组织中 NF-κB表达的影响

目的：观察白屈菜赤碱对大鼠肺组织形态的长期毒性作用及其对大鼠肺组织中核转录因子κB （NF-κB）表达的影响,探讨其引起大鼠肺损伤的相关机制。方法：将120只Wistar大鼠随机分为对照组（给予生理盐水）和低、中及高剂量白屈菜赤碱组（给予3.7、5.6和8.4 mg·kg^-1白屈菜赤碱）,每组30只。观察各组大鼠一般情况;HE染色观察各组大鼠肺组织形态表现;酶联免疫吸附（ELISA）法检测各组大鼠血清白细胞介素6（IL-6）、白细胞介素8（IL-8）和肿瘤坏死因子α（TNF-α）水平;实时荧光定量PCR法检测各组大鼠肺组织中NF-κB和细胞间黏附分子1（ICAM-1） mRNA表达水平;Western blotting法检测各组大鼠肺组织中NF-κB和ICAM-1蛋白表达水平。结果：高剂量白屈菜赤碱组大鼠累积死亡率最高,其次为中和低剂量白屈菜赤碱组。各剂量白屈菜赤碱组大鼠体质量和摄食量均明显低于对照组（P<0.05）,高剂量白屈菜赤碱组大鼠体质量和摄食量低于低和中剂量白屈菜赤碱组（P<0.05）。白屈菜赤碱能引起大鼠肺充血和血性腹水。HE染色,随着白屈菜赤碱剂量的增加,各剂量白屈莱赤碱组大鼠肺组织损伤加重。与对照组比较,各剂量白屈菜赤碱组大鼠血清IL-6、IL-8和TNF-α水平升高（P<0.05）;与低和中剂量白屈菜赤碱组比较,高剂量白屈菜赤碱组大鼠血清IL-6、IL-8和TNF-α水平升高（P<0.05）。与对照组比较,各剂量白屈菜赤碱组大鼠肺组织中NF-κB和ICAM-1 mRNA和蛋白表达水平升高（P<0.05）,并呈剂量依赖性;与低和中剂量白屈菜赤碱组比较,高剂量白屈菜赤碱组大鼠肺组织中NF-κB和ICAM-1 mRNA和蛋白表达水平升高（P<0.05）。结论：白屈菜赤碱以剂量依赖的方式对大鼠肺组织产生长期毒性作用,中和高剂量白屈菜赤碱可能通过NF-κB活化和产生炎性细胞因子加重中毒性肺损伤。     

姜黄素对脂多糖诱导大鼠急性肺损伤的保护作用

目的观察姜黄素对脂多糖诱导大鼠急性肺损伤（ALI）的保护作用。方法 Wistar大鼠随机分为6组：空白组、模型组、地塞米松组和姜黄素三个不同剂量组（50、100、200mg.kg-1）。LPS气管滴注复制ALI模型,6h后收集支气管肺泡灌洗液（BALF）,检测TNF-α、IL-1β浓度及蛋白含量;称重法检测肺组织湿/干重比和肺含水量。结果姜黄素剂量依赖性降低LPS所致ALI模型BALF中TNF-α、IL-1β及蛋白量增加,降低肺湿/干重比、肺含水量。结论姜黄素对LPS所致ALI有保护作用,其可能的机制为调节炎症介质的产生有关。     

N-乙酰半胱氨酸对PM2.5致大鼠睾丸毒性的保护作用

目的 探讨N-乙酰半胱氨酸(N-acetylcysteine,NAC)改善亚急性暴露于大气细颗粒物(particulate matter,PM)2.5致大鼠睾丸损伤的作用。 方法 30只 Wistar大鼠随机分为3组,分别为生理盐水对照组、PM2.5暴露组、PM2.5+N-乙酰半胱氨酸组。通过气管内滴注的方法进行染毒,每次剂量为5.0 mg/kg,每周染毒一次,共8周;NAC组在PM2.5染毒的基础上,通过灌胃方式连续给予150 mg·kg-1·d-1 NAC;生理盐水对照组通过气管内滴注同体积生理盐水（1 mL/kg）作为对照。造模后HE染色制作睾丸组织病理切片,TUNEL法检测睾丸凋亡情况,分光光度计法检测睾丸组织超氧化物歧化酶（superoxide dismutase,SOD）、谷胱甘肽（glutathione,GSH）、和丙二醛（malondialdehyde,MDA）指标,酶联免疫吸附测定（enzyme-linked immunosorbent assay,ELISA）法测定睾丸白细胞介素10(interleukin-10,IL-10)及睾酮水平。 结果 PM2.5暴露组和PM2.5+NAC组大鼠血清睾酮水平及睾丸组织GSH、SOD、IL-10水平均低于盐水对照组,睾丸组织MDA水平升高,PM2.5+NAC组睾酮水平及睾丸组织GSH、SOD、IL-10水平高于PM2.5组,睾丸组织MDA水平下降(P＜0.05)。在PM2.5暴露组中,曲精小管中多个细胞核表现出明显的深棕色染色,TUNEL阳性细胞的计数明显高于盐水对照组和PM2.5+NAC组(P＜0.05);而PM2.5+NAC组凋亡细胞数明显低于PM2.5组,但高于盐水对照组(P＜0.05)。PM2.5暴露组和PM2.5+NAC组睾丸细胞凋亡指数高于盐水对照组,PM2.5+NAC组低于PM2.5暴露组(P＜0.05)。 结论 PM2.5亚急性暴露可以造成大鼠睾丸组织病理损伤,诱导睾丸细胞凋亡,引起氧化炎症指标改变,而NAC作为一种抗氧化剂,可以明显改善上述损伤作用,对PM2.5致睾丸毒性作用具有拮抗作用。     

PM2．5对被动吸烟大鼠慢性气道炎症及氧化应激反应的影响

目的探讨PM2．5短期暴露对被动吸烟大鼠慢性气道炎症和氧化应激反应的影响及可能机制。方法48只雄性Wistar大鼠分为正常对照组（n=12）和被动吸烟模型组（n=36）,后者在给予被动吸烟45d后再随机分为单纯被动吸烟组、低剂量（1．25mg／mL）PM2.5暴露组和高剂量（5mg／mL）PM2．5暴露组（n=12）。在末次PM2．5染毒24h时点,测定大鼠肺功能;收集支气管-肺泡灌洗液（BALF）,细胞涂片及吉姆萨（Giemsa）染色后进行细胞计数及分类,对BALF中自介素-6（IL-6）、丙二醛（MDA）、总抗氧化能力（T-AOC）、谷胱甘肽过氧化物酶（GSH—Px）和过氧化氢酶（CAT）等指标进行检测;取左肺上叶肺组织,利用光学显微镜（光镜）和透射电子显微镜（透射电镜）观察肺组织学改变和细胞超微结构。结果单纯被动吸烟组和PM2．5暴露组BALF中自细胞总数均显著高于正常对照组（P〈0．05）,高剂量PM2．5暴露组中性粒细胞百分比显著高于低剂量PM2．5暴露组（P〈0．05）。随着PM2．5暴露浓度的升高,大鼠肺功能参数显著降低（P〈0．05）。与正常对照组比较,单纯被动吸烟组和PM2．5暴露组BALF中IL-6和MDA水平显著升高,T-AOC、GSH—Px和CAT水平显著降低,差异均有统计学意义（P〈0．05）;与单纯被动吸烟组比较,高剂量PM2．5暴露组IL-6和MDA水平显著升高,T-AOC、GSH—Px和CAT水平显著降低,差异均有统计学意义（P〈0．05）。光镜观察可见单纯被动吸烟组大鼠的支气管壁、血管腔及小气道内中性粒细胞、淋巴细胞、巨噬细胞及嗜酸性粒细胞浸润,肺泡间隔明显变薄或融合,肺泡腔内渗出、充血,肺泡管扩张等结构破坏;PM2.5暴露组上述炎症过程进一步加剧,透射电镜观察发现巨噬细胞和肺泡Ⅱ型上皮细胞超微结构发生明显改变。结论PM2．5短期暴露可加重被动吸烟大鼠气道慢性炎症及氧化应激反应。     

Role of tumor necrosis factor-alpha and interleukin-1beta on lung dysfunction following hemorrhagic shock in rats.

BACKGROUND: Hemorrhagic shock occasionally causes a fatal outcome following an outbreak of lung dysfunction, but the precise mechanism has not been clearly elucidated. Several studies have indicated that hemorrhagic shock causes a delayed vascular inflammatory decompensation and leads to inflammation-related organ dysfunction. Tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta are known as major proinflammatory cytokines that play an important role in excessive autolytic inflammation, finally inducing organ dysfunctions. In this study, the role of TNF-alpha and IL-1beta on lung dysfunction following hemorrhagic shock was examined by using FR167653, a potent inhibitor of TNF-alpha and IL-1beta production that acts by suppressing p38 mitogen-activated protein kinase (MAPK). MATERIAL/METHODS: Hemorrhagic shock was induced in anesthetized male rats by bleeding via a common carotid catheter for 20 minutes to 25% of total body blood volume without fluid resuscitation. Mean blood pressure, heart rate and arterial blood gas components were recorded up to 5 hours after the bleeding. The levels of TNF-alpha, IL-1beta and lactic dehydrogenase (LDH)-3 isozyme were measured in the serum of pulmonary venous blood. The lung tissue was excised for the assay of mRNA and for histopathological study. RESULTS: The expressions of mRNA for TNF-alpha and IL-1beta in the lung tissue and the concentrations of both cytokines in pulmonary serum increased after a hemorrhage. Inflammation-related injuries and function deterioration were observed in the lung following hemorrhagic shock. These hemorrhagic changes were inhibited by pretreatment with FR167653. CONCLUSIONS: TNF-alpha and IL-1beta play a key role in the development of inflammation-related lung dysfunction following hemorrhagic shock. Our model should be useful to explain the pathogenesis of lung dysfunction following hemorrhagic shock.     

糖皮质激素对内毒素致急性肺损伤大鼠肺组织Fractalkine表达的影响

目的动态观察内毒素（LPS）所致急性肺损伤（acute lung injury，ALI）大鼠肺组织内趋化因子Fractalkine（FKN）的表达变化，及糖皮质激素对其的影响。方法将42只大鼠随机分为空白对照组、模型组（LPS）及地塞米松干预组（DEX），其中LPS组和DEX组再分为1h、2h、4h3个时相组，每组6只，LPS组和DEX组大鼠经尾静脉注射LPS（4mg／kg）建立ALI大鼠模型。采用ELISA、RT—PCR等方法，观察ALI大鼠模型肺组织病理学改变、肺湿干重比值（W／D）及血清TNF-a变化，并检测肺组织FKNmRNA的表达，同时观察地塞米松对上述指标的影响．结果模型组1h、2h与4h3个时相组肺损伤病理改变、肺W／D、血浆TNF—α均明显增高，地塞米松能减轻ALl大鼠肺组织炎症反应、肺W／D值及血清TNF—α水平（P均〈0．05）。正常大鼠肺组织FKNmRNA有表达，模型组3个时相亚组肺组织FKNmRNA表达较正常组明显增加（P〈0．05），在2h时点达峰值，地塞米松能下调ALI大鼠肺组织FKNmRNA表达（P〈0．05）。FKNmRNA的表达量与血清TNF—α水平呈正相关（r=0．674，P〈0．05）．结论早期应用地塞米松可降低TNF-α水平，下调肺组织FKN mRNA的表达，这可能是糖皮质激素对内毒素致急性肺损伤实验大鼠保护作用机制之一。     

异丙肾上腺素对高血压患者单核细胞分泌白细胞介素6及肿瘤坏死因子α的影响

目的:观察异丙肾上腺素(isoproterenol, ISO)对高血压患者单核细胞分泌肿瘤坏死因子α(tumor necrosis factor-alpha ,TNF-α)及白细胞介素6(interleukin-6, IL-6)的影响.方法:选取17例健康志愿者和6例原发性高血压病患者(Ⅰ期)的静脉血样,分离得到单核细胞,用脂多糖(lipopolysaccharide,LPS)刺激细胞后,检测在有或无ISO存在条件下细胞上清液中TNF-α和IL-6含量.结果:(1)在LPS刺激下,高血压组单核细胞分泌TNF-α量较健康对照组显著增加[(1 897±393) ng/L vs. (975±473) ng/L, P＜0.01],但IL-6的分泌在两组间的差异无统计学意义[(5 532±796) ng/L vs. (6 092±2 249) ng/L];(2)在健康对照组和高血压组中,ISO能剂量依赖性抑制LPS引起的单核细胞TNF-α分泌,但对IL-6的分泌则无显著影响;(3)在Ⅰ期高血压患者的单核细胞中,ISO对TNF-α产生的抑制作用与健康对照组相比,差异无统计学意义(P》0.05),给予β肾上腺素受体拮抗剂普萘洛尔可拮抗这种效应.结论:β肾上腺素受体激动可抑制LPS引起单核细胞分泌TNF-α,而对IL-6的分泌无影响,这种抑制效应在Ⅰ期高血压病患者与健康志愿者之间差异无统计学意义.     

原花青素B2对PM2.5急性暴露致大鼠心脏毒性的保护作用

目的 探讨原花青素B2(procyanidin B2,PCB2)对PM2.5急性暴露致大鼠心脏毒性的保护作用.方法 24只雄性健康成年SD大鼠按照随机数字表法分为三组:生理盐水对照组(持续三蒸水灌胃21 d,在第8天、第10天、第12天气管滴注生理盐水)、PM2.5组(持续三蒸水灌胃21 d,在第8天、第10天、第12...     

风湿之邪对寒邪犯肺证大鼠肺脏细胞因子的影响

目的：研究风湿之邪对不同温度梯度变化的寒邪犯肺证大鼠肺脏组织中肿瘤坏死因子α（tumor necrosis factor—α，TNF-α）、白细胞介素6（interleukin-6，IL-6）、白细胞介素4（interleukin-4，IL-4）、γ干扰素（interferon-γ，IFN-γ）等细胞因子的影响。 方法：将104只SPF级Wistar大鼠随机分为13组：常温对照组、寒邪6组和风寒湿邪（寒邪夹5级左右风力，相对湿度为90％～100％）6组，寒邪包括恒定低温（10℃、0℃、－10℃）和温差（20～10℃、20～0℃、20～－10℃）。第1天将大鼠置于相应环境的调温箱中饲养2h后取出，置常温下饲养4d，观察大鼠的整体状况。放射免疫法测肺组织匀浆中TNF—α、IL－6和IL－4含量，酶联免疫吸附试验检测肺组织匀浆中IFN－γ含量。 结果：与相同温度的寒邪组相比，风寒湿各组大鼠肺组织匀浆中TNF—α、IL－6和IL－4水平明显升高（P〈0．01），IFN—γ水平显著下降（P〈0．01），IFN-γ／IL－4比值显著下降（P〈0．01）。 结论：风湿之邪能够明显加重寒邪对肺脏的损害，加重寒邪犯肺所导致的机体Th1／Th2免疫应答失衡。     

内异方对子宫内膜异位症大鼠细胞因子含量、血管内皮细胞生长因子mRNA表达的影响

目的：探讨中药内异方对子宫内膜异位症大鼠细胞因子含量及血管内皮细胞生长因子（VEGF）mRNA表达的调节作用。方法：用Cummings AM方法复制子宫内膜异位症动物模型，采用ELISA法检测IL－6、IL－8、IL－10含量，Dot blot法检测VEGF mRNA表达水平。结果：模型组外周血IL－6、腹腔液IL－8水平、腹腔巨噬细胞数量及巨噬细胞在脂多糖（LPS）刺激下产生的IL－6含量显高于正常对照组；内异方组异位种植内膜组腹腔巨噬细胞在LPS刺激下产生的IL－10含量显低于正常对照组和内异方组；模型组种植异位内膜组织VEGF mRNA表达水平明显高于内异方组。结论：子宫内膜异位症细胞因子IL－6、IL－8、IL－10的失衡与疾病的发生发展有关，VEGF mRNA的过度表达与内异灶血管的形成相关；内异方可显抑制异位内膜组织的生长，同时抑制异位灶VEGF mRNA的过度表达，减少异位灶血管的生成，并对细胞因子有明显的调节作用。     

Role of Shenfu Injection (参附注射液) in rats with systemic inflammatory response syndrome

Objective： To investigate the role of Shenfu Injection （参附注射液, SFI） in rats with systemic inflammatory response syndrome （SIRS）. Methods： The SIRS rat model was induced by the intravenous injection of lipopolysaccharide （LPS）. Forty-five male Wistar rats were randomly divided into 3 groups, the sham operative control group （control group, n=5）, the SIRS model group （model group, n=20） and the SFI treatment group （SFI group, n=20）. LPS was injected through the external jugular vein （12 mg/kg, 6 mg/mL） to all rats except for those in the control group, and SFI （10 mL/kg） was given to those in the SF group only once through intraperitoneal injection, while the normal saline （10 mL/kg） was given to those in the model group. For those in the control group, normal saline was given through the external jugular vein （2 mL/kg） and intraperitoneal injection （10 mL/kg）. Then, rats in the model group and SFI group were divided into 4 subgroups according to the time points, i.e., 1 h, 2 h, 4 h and 6 h subgroups, 5 rats in each group. The activity of nuclear factor of κB （NF-κB） of in blood mononuclear cells and the plasma levels of tumor necrosis factor- α （TNF- α ） and interleukin 6-（IL-6） were determined using enzyme-linked immunoabsordent assay （ELISA） at 1 h, 2 h, 4 h and 6 h after modeling. Histopathologic changes of the lung and liver were observed under a light microscope. Results： Compared with the control group, the activity of NF-κB in mononuclear cells and the plasma level of TNF-α were obviously increased at each time points （all P〈0.01）, reaching the peaks at 2 h after modeling. The plasma level of IL-6 increased gradually as time went by in the model group （P〈0.01）. Pathological examination showed pulmonary alveoli hemorrhage, edema and inflammatory cell infiltration in the lung tissue, and angiotelectasis, congestion, and local necrosis in the liver tissue in the model group. Compared with the model group, the activity     

β-carotene protects rats against bronchitis induced by cigarette smoking

Objective To investigate the protective effects of B-carotene in rats against the development of chronic bronchitis induced by cigarette smoking.Methods Forty-two Male Wistar rats were randomly divided into three study groups: ①control (n =15), animals underwent no treatment; ②cigarette smoking (n = 15), animals developed chronic bronchitis through long-term cigarette smoking twice a day for 75 d; ③β-carotene plus cigarette smoking animals (n =12) were given 1 ml or 15 mg/kg β-carotene orally every day just before cigarette smoking. The levels of IL-6, IL-8, NO, superoxide dismutase (SOD) and lipoperoxide(LPO) in serum, bronchoalveolar lavage fluid (BALF) and lung tissue were measured and the pathological changes to lung tissue were analyzed using light microscopy.Fiesults Long-term cigarette smoking caused an obvious increase in the amount of IL-6, IL-8 and LPO and a sharp decrease in the levels of NO and SOD in smoking animals compared to controls. β-carotene intake reversed all the changes induced by smoking and alleviated the pathological changes caused by chronic bronchitis.Conclusions Quantitative oral intake of B-carotene had protective effects against chronic bronchitis induced by long-term cigarette smoking, which was associated with the increased production of NO,the clearance of some oxidative free radicals (OFR) and the alleviation of chronic inflammation.     

蝉芩颗粒对神经生长因子介导的PM2.5所致大鼠气道神经源性炎症的影响

【目的】探讨蝉芩颗粒对神经生长因子(NGF)介导的PM2.5所致气道神经炎症的影响及其作用机制。【方法】将40只SD大鼠随机分为5组,即盐水对照组、PM2.5染毒组、抗NGF组、蝉芩颗粒组、惠菲宁组,每组8只。复制PM2.5大鼠气道滴注染毒模型。PM2.5染毒组大鼠染毒后给予等体积生理盐水灌胃,抗NGF组抗NGF干预染毒后给予生理盐水灌胃,蝉芩颗粒组染毒后予蝉芩颗粒(9.36 g·kg~(-1)·d~(-1))灌胃,惠菲宁组染毒后予惠菲宁糖浆(8 mL·kg~(-1)·d~(-1))灌胃,盐水对照组大鼠以生理盐水代替PM2.5气道灌注后给予等体积生理盐水灌胃,共2周。给药结束后,采用酶联免疫吸附(ELISA)法检测各组大鼠血清中P物质(SP)、降钙素基因相关肽(CGRP)、速激肽A(NKA)、速激肽B(NKB)、NGF的含量,采用免疫组化法检测各组大鼠肺组织、背根神经节中SP、NGF的表达,分别采用免疫印迹(Western blot)法及实时荧光定量逆转录—聚合酶链反应(RT-qPCR)法检测各组大鼠肺组织、背根神经节中NGF蛋白和m RNA的表达。【结果】与盐水对照组比较,染毒组大鼠血清中SP、CGRP、NKA、NKB、NGF值,肺组织NGF,背根神经节SP、NGF的免疫组化平均光密度值,肺组织中NGF蛋白和m RNA及背根神经节中NGF蛋白的表达水平均显著升高(P0.05);与染毒组比较,抗NGF组、蝉芩颗粒组、惠菲宁组上述指标均显著降低(P0.05),但3组比较,差异无统计学意义(P0.05)。【结论】蝉芩颗粒可通过抑制NGF的表达减轻PM2.5所致大鼠气道神经源性炎症。     

Antagonistic Effects of N-acetylcysteine on Mitogen-activated Protein Kinase Pathway Activation,Oxidative Stress and Inflammatory Responses in Rats with PM2.5 Induced Lung Injuries

Objective To evaluate the antagonistic effects of N-acetylcysteine (NAC) on mitogen-activated protein kinases (MAPK) pathway activation, oxidative stress and inflammatory responses in rats with lung injury induced by fine particulate matter (PM_2.5).Methods Forty eight male Wistar rats were randomly divided into six groups: blank control group (C1), water drip control group (C2), PM_2.5 exposed group (P), low-dose NAC treated and PM_2.5 exposed group (L), middle-dose NAC treated and PM_2.5 exposed group (M), and high-dose NAC treated and PM_2.5 exposed group (H). PM_2.5 suspension (7.5 mg/kg) was administered tracheally once a week for four times. NAC of 125 mg/kg, 250 mg/kg and 500 mg/kg was delivered intragastrically to L, M and H group respectively by gavage (10 ml/kg) for six days before PM_2.5 exposure. The histopathological changes and human mucin 5 subtype AC (MUC5AC) content in lung tissue of rats were evaluated. We investigated IL-6 in serum and bronchoalveolar lavage fluid (BALF) by Enzyme-linked immunosorbent assay (ELISA), MUC5AC in lung tissue homogenate by ELISA, glutathione peroxidase (GSH-PX) in serum and BALF by spectrophotometry, and the expression of p-ERK1/2, p-JNK1/2 and p-p38 proteins by Western blot. All the measurements were analyzed and compared statistically.Results Lung tissue of rats exposed to PM_2.5 showed histological destruction and increased mucus secretion of bronchial epithelial cells. Rats receiving NAC treatment showed less histological destruction and mucus secretion. Of P, L, M and H group, MUC5AC in lung tissue, IL-6 in serum and BALF were higher than controls (C1 and C2) (all P<0.05), with the highest levels found in the P group and a decreasing trend with increase of NAC dose. The activity of GSH-PX in serum and BALF of PM_2.5 exposed rats (P, L, M and H) was lower than that of controls (all P<0.05), with higher activities found in NAC treated rats (L, M, and H), and an increasing trend with increase of NAC dose. The expressions of p-ERK1/2, p-JNK1/2 and p-p38 proteins in PM_2.5 exposed lung tissue (P, L, M and H) was higher than controls (all P<0.05), with decreased levels and dose dependent downregulation found in NAC treated rats.Conclusion NAC can antagonize major MAPK pathway activation, lung oxidative stress and inflammatory injury induced by PM_2.5 in rats.     

大气细颗粒物对大鼠白细胞介素17表达的影响及连花清瘟的干预作用

目的  探讨大气细颗粒物（PM2.5）急性暴露对大鼠肺部损伤的作用,及高、中、低剂量连花清瘟对其的保护作用。方法  48只Wistar大鼠,随机分为4个实验组（PM2.5染尘组及高、中、低剂量连花清瘟干预组）和2个对照组（空白对照组及生理盐水对照组）。由石家庄市环境监测中心提供空气细颗粒物,制备PM2.5悬液,采用气管内滴注法。空白对照组无任何干预措施;生理盐水对照组给予气管滴注生理盐水（1 ml/kg）;染尘组给予一次性气管内滴入PM2.5悬液（7.5 mg/kg）;3组干预组首先分别连续灌胃给予低（生药2 g/kg）、中（生药4 g/kg）、高（生药8 g/kg）剂量的连花清瘟溶液4 d,第4天灌胃给药后分别经气管滴入PM2.5悬液（7.5 mg/kg)。应用酶联免疫分析（ELISA）法测定各实验组动物血清白细胞介素17（IL-17)及肺表面活性蛋白A（SP-A）水平,并在光镜下观察肺组织病理形态变化。结果  空白对照组和生理盐水对照组间血清IL-17及SP-A差异无统计学意义（P >0.05）,染尘组血清IL-17及SP-A水平较生理盐水对照组及空白对照组显著升高,差异有统计学意义（P <0.05）;高、中、低剂量干预组较染尘组血清IL-17及SP-A水平均有不同程度降低,中高剂量组差异有统计学意义（P <0.05）。结论  PM2.5急性暴露可以导致大鼠肺部损伤,连花清瘟对肺部损伤有保护作用。

     

大鼠小体积肝移植后早期肺组织内炎症因子的表达及其意义

目的　探讨大鼠小体积肝移植后早期肺组织内肿瘤坏死因子α(TNFα)、白细胞介素 1β(IL 1β)及细胞间粘附分子 1(ICAM 1)mRNA的表达及其意义。 方法　用 15 0只大鼠建立全肝、5 0 %及 30 %小体积肝移植模型 ,分别于术后 0 5、2、6和 2 4h处死大鼠 ,同时以假手术组作为对照。ELISA法检测血浆TNFα含量 ,RT PCR方法检测肺组织内TNFα、IL 1β及ICAM 1mRNA表达 ,比色法检测肺组织内髓过氧化物酶 (MPO)的活性 ,同时行常规病理学检查。结果　 (1)血浆TNFα高峰出现于术后 2h ,全肝移植组在移植后 2h高于 30 %肝移植组 (P <0 0 5 )。 (2 )全肝移植组和 5 0 %肝移植组TNFαmRNA表达在移植后 2h和 6h表达水平均高于 30 %肝移植组和假手术组 (P <0 0 1,P <0 0 5 ) ,其表达高峰均出现在术后 2 4h ;假手术组IL 1βmRNA无表达 ,肝移植组呈中等强度表达 ,但各组在各时点差异无显著意义 ;移植组在各时点ICAM 1mRNA表达均高于假手术组 (P<0 0 1,P <0 0 5 ) ,但各移植组间在各时点的差异无显著意义。 (3)MPO活性 :移植各组均高于假手术组 (P <0 0 1) ,全肝和 5 0 %肝移植组活性高峰出现于移植后 2h ,而 30 %肝移植组出现于移植后 6h ,且血浆TNFα水平与肺组织MPO活性呈正相关 (r =0 4 2 2 ,P <0 0 5 )。 (4 )病     

7,3′-二甲氧基橙皮素对佐剂性关节炎大鼠免疫功能的影响

目的研究7,3’-二甲氧基橙皮素(DMHP)对佐剂性关节炎(AA)大鼠免疫功能的影响。方法弗氏完全佐剂诱导大鼠AA模型,从造模第12天开始灌胃给予DMHP(22、44、88 mg/kg),连续12 d,MTT法检测刀豆蛋白A诱导的脾淋巴细胞增殖反应;酶联免疫吸附法测定脾淋巴细胞产生白介素-2(IL-2)的水平以及腹腔巨噬细胞(PMΦ)分泌的IL-1、IL-10、肿瘤坏死因子-α(TNF-α)水平;RT-PCR检测PMΦIL-1、IL-10、TNF-αmRNA的表达。结果 DMHP(44、88 mg/kg)能明显纠正AA大鼠低下的脾淋巴细胞增殖反应和脾细胞IL-2的产生;各剂量DMHP能不同程度地从基因和蛋白水平降低AA大鼠PMΦ产生过高的IL-1、TNF-α水平,同时上调AA大鼠PMΦ产生过低的IL-10水平。结论 DMHP体内给药能改善AA大鼠异常免疫功能,恢复细胞因子网络平衡,这可能是其治疗AA大鼠的机制之一。