鸦胆子与补骨脂治疗大鼠卡氏肺孢子虫肺炎的研究

目的研究中药鸦胆子和补骨脂对卡氏肺孢子虫肺炎病鼠的治疗作用。方法用地塞米松皮下注射SD大鼠6周，建立卡氏肺孢子虫肺炎动物模型。用中药鸦胆子与补骨脂合剂治疗大鼠，设立1周治疗组、2周治疗组、阳性对照组1、阳性对照组2和健康对照组。观察大鼠体重、肺组织病理、肺印片中每视野虫体包囊均数及血液CD4^＋和CD8^＋T细胞、IFN-γ的动态变化。结果鸦胆子和补骨脂合剂治疗组大鼠体重回升，1周治疗组和2周治疗组体重回升率分别达到26．85％和31．77％；肺组织虫体包囊数目明显减少或消失，两个治疗组包囊减少率分别为94．44％和98．15％；血液CD4^＋、CD8^＋T细胞和IFN-γ水平较阳性对照组升高，其中CD4^＋T细胞和IFN-γ显著升高（P〈0．05）。结论中药鸦胆子和补骨脂对卡氏肺孢子虫肺炎大鼠有明显的治疗效果．     

保元汤加减对卡氏肺孢子虫肺炎模型大鼠的免疫调节作用初探

目的 观察中药保元汤加减煎剂对卡氏肺孢子虫肺炎模型大鼠免疫状态的调节作用，以探索中医药治疗卡氏肺孢子虫肺炎的新途径。方法 在造模不同时间，以保元汤加减煎剂给卡氏肺孢子虫肺炎(PCP)模型大鼠灌胃，2ml／次，1次／d，于造模后第8周末，测定各组实验大鼠淋巴细胞转化率及T细胞亚群百分率。结果 预防组大鼠淋巴细胞转化率明显高于PCP模型对照组，其值与正常对照组差异无显著性；预防组和治疗组大鼠的CD4^ 及CD4^ ／CD8^ 值高于PCP模型对照组和治疗对照组，预防组CD4^ 及CD4^ ／CD8^ 值与正常对照组差异无显著性。结论保元汤加减煎剂，可提高卡氏肺孢子虫肺炎模型大鼠的机体免疫功能，可作为防治卡氏肺孢虫子肺炎的药物。     

保元汤加减对卡氏肺孢子虫肺炎模型大鼠的免疫调节作用初探

目的　观察中药保元汤加减煎剂对卡氏肺孢子虫肺炎模型大鼠免疫状态的调节作用 ,以探索中医药治疗卡氏肺孢子虫肺炎的新途径。　方法　在造模不同时间 ,以保元汤加减煎剂给卡氏肺孢子虫肺炎 (PCP)模型大鼠灌胃 ,2ml/次 ,1次 /d ,于造模后第 8周末 ,测定各组实验大鼠淋巴细胞转化率及T细胞亚群百分率。　结果　预防组大鼠淋巴细胞转化率明显高于PCP模型对照组 ,其值与正常对照组差异无显著性 ;预防组和治疗组大鼠的CD4+ 及CD4+ /CD8+ 值高于PCP模型对照组和治疗对照组 ,预防组CD4+ 及CD4+ /CD8+ 值与正常对照组差异无显著性。　结论　保元汤加减煎剂 ,可提高卡氏肺孢子虫肺炎模型大鼠的机体免疫功能 ,可作为防治卡氏肺孢虫子肺炎的药物。     

蒿甲醚用于卡氏肺孢子虫肺炎大鼠的治疗及其对IL-6影响的研究

目的 从病理学和细胞因子角度探讨蒿甲醚对大鼠卡氏肺孢子虫肺炎（Pneumocystiscarinii Pneumonia POP）的治疗效果和作用机理。方法 给SD大鼠皮下注射地塞米松磷酸钠建立卡氏肺孢子虫肺炎动物模型，治疗组给予蒿甲醚治疗。ELISA双抗夹心法分别检测血清和支气管肺泡灌洗液中1L-6水平。结果 与感染对照组比较，蒿甲醚治疗组症状显著改善、肺印片中卡氏肺孢子虫包囊数目显著减少、肺组织炎症明显减轻、血清和肺泡灌洗液中IL-6水平明显下降。结论 蒿甲醚具有一定抗大鼠卡氏肺孢子虫肺炎作用，能够降低PCP大鼠IL-6。     

中药鸦胆子与补骨脂素对卡氏肺孢子虫病大鼠免疫调节的影响

目的 探讨中药鸦胆子和补骨脂素合剂对卡氏肺孢子虫肺炎(PCP)大鼠的免疫调节及杀虫作用。方法 地塞米松皮下注射SD大鼠(2.5mg/只,每周2次,连续6周),建立PCP大鼠模型。药物治疗剂量,每鼠每天口饲中药鸦胆子0.12mg与补骨脂素1mg,连续7d或14d。同时设PCP阳性不治疗对照组及正常大鼠对照组。制作肺组织病理切片观察肺组织病变,制作肺组织印片计数肺孢子虫包囊数观察中药合剂杀虫效果。检测血液中CD4⁺T细胞、CD8+T细胞和α肿瘤坏死因子(TNF-α)的变化,观察中药合剂对PCP大鼠的免疫调节作用。结果 治疗组大鼠,受损的肺组织病变减轻或修复,体重明显回升,肺组织包囊数明显低于阳性对照组(P<0.05)。血液中CD4⁺T细胞、CD8⁺T细胞和TNF-α均较阳性对照组升高(P<0.05)。结论 中药鸦胆子和补骨脂素合剂治疗PCP大鼠,可增强免疫调节作用,并可抑制及杀灭卡氏肺孢子虫。     

鸦胆子与补骨脂对大鼠卡氏肺孢子虫肺炎疗效的电镜观察

用鸦胆子和补骨脂合剂2 ml （鸦胆子0.12 mg+补骨脂1.0 mg） 分别治疗经地塞米松皮下注射诱导的卡氏肺孢子虫肺炎（Pneumocystis carinii pneumonia， PCP）的SD大鼠7天和14天，同时设阳性对照组和正常对照组。分别于治疗后剖杀各组大鼠，取肺组织制成切片。透射电镜下观察到治疗组大鼠受损肺组织病变减轻，肺间质、Ⅰ型和Ⅱ型肺泡上皮细胞形态结构修复。说明鸦胆子和补骨脂合剂对卡氏肺孢子虫肺炎病鼠有一定的疗效。     

双氢青蒿素哌喹对大鼠肺孢子虫肺炎的治疗效果

目的观察双氢青蒿素哌喹（科泰复）对大鼠肺孢子虫肺炎（PCP）的治疗效果，并探讨其可能的作用机理。方法以每周2次连续6周皮下注射地塞米松诱导SD清洁级大鼠建立肺孢子虫肺炎动物模型，采用科泰复40mg／kg，连续3d，双氢青蒿素（科泰新）60mg／kg，连续6d治疗实验大鼠，以复方新诺明为治疗对照组，通过存活率、体重回升率、肺重／体重比、肺印片的每视野包囊均数、大鼠外周血CD4^＋、CD8^＋T细胞亚群和血清一氧化氮（NO）、γ-干扰素（IFN-γ）、α-肿瘤坏死因子（TNF-α水平等指标考核其疗效。结果科泰复、科泰新治疗组的大鼠存活率提高，治疗后大鼠体重增加，肺重／体重比、肺印片的每视野包囊均数和血清NO和TNF-α水平均显著低于PCP模型阳性对照组（P〈0．05），而科泰复和科泰新治疗组大鼠外周血CD4^＋T淋巴细胞亚群和IFN-γ水平则均显著高于PCP模型阳性对照组（P〈0．05）。结论科泰复、科泰新对大鼠肺孢子虫肺炎具有治疗和免疫调节作用。     

采用不同的免疫抑制方法诱发大鼠卡氏肺孢子虫感染的研究

卡氏肺孢子虫肺炎是一种常见的机会感染,多见于免疫缺陷及免疫抑制患者。为进一步研究卡氏肺孢子虫生物学特性,我们采用给大鼠大剂量免疫抑制剂、■Co 辐照及幼大鼠胸腺切除三种不同的免疫抑制方法成功地诱发大鼠卡氏肺孢子虫显性感染。     

双氢青蒿素对卡氏肺孢子虫超微结构的影响

目的　观察双氢青蒿素对卡氏肺孢子虫超微结构的影响。方法　以醋酸可的松皮下注射 Wistar大鼠 6周 ,诱导建立肺孢子虫肺炎动物模型 ,用双氢青蒿素治疗大鼠 ,并用电镜观察大鼠肺切片中肺孢子虫超微结构。结果　双氢青蒿素可使肺孢子虫滋养体胞浆及包囊内出现空泡 ,线粒体肿胀、核膜破裂、内质网肿胀 ,囊内小体溶解破坏等超微结构改变。结论　双氢青蒿素主要对卡氏肺孢子虫膜系结构产生破坏作用     

卡氏肺孢子虫病鼠氧化损害与中药防治的实验研究

目的探讨卡氏肺孢子虫感染大鼠后所致组织氧化损害与发病的关系及中药防治的实验研究。方法观察大鼠感染卡氏肺孢子虫后,经鸦胆子、补骨脂及两者合剂治疗前后,肺、脑组织感染虫数、病理以及GSH、MDA、XOD三项检测指标的变化。结果病鼠肺组织印片中有大量原虫,镜下观肺泡壁充血和炎性细胞浸润,肺泡腔内有大量炎性渗出液,一些病灶呈实变观。肺组织和脑组织中MDA和XOD升高,而GSH下降,经治疗后肺泡壁充血减轻,肺泡及肺泡间质中炎性渗出物和炎性细胞减少。鸦胆子及合剂治疗组清除氧自由基能力较强。结论卡氏肺孢子虫病鼠发病除与虫体本身所致肺组织的炎性损伤外,还可能与该虫体在宿主组织内引发多种氧化酶类产生严重的氧自由基损害有关,鸦胆子及补骨脂对大鼠肺孢子虫肺炎具有一定的防治效果。     

苦参合剂对隐孢子虫感染大鼠细胞免疫功能的影响

目的　探讨苦参合剂对隐孢子虫（ＣＰＳ）感染大鼠细胞免疫功能的影响。方法　建立大鼠ＣＰＳ感染模型,实验第１～１７ 天给动物口饲苦参合剂。结果　３ｍ ｌ／（ｋｇ·ｄ）苦参合剂组的ＣＤ３＋ 和ＣＤ４＋ 细胞百分率以及白细胞总数与淋巴细胞计数均明显高于非治疗组（Ｐ＜ ０．０１）且与健康对照组无差异（Ｐ＞ ０．０５）,１５ｍ ｌ／（ｋｇ·ｄ）苦参合剂组无上述效果。非治疗组的ＣＤ３＋和ＣＤ４＋ 百分率和白细胞数及淋巴细胞数均明显低于单纯地塞米松组（Ｐ＜ ０．０１）。结论　３ｍ ｌ／（ｋｇ·ｄ）苦参合剂能增强大鼠的细胞免疫功能,而１５ｍ ｌ／（ｋｇ·ｄ）苦参合剂无上述作用;隐孢子虫感染可降低宿主的免疫功能     

Impact of bacterial pneumonia and Pneumocystis carinii pneumonia on human immunodeficiency virus disease progression. Pulmonary Complications of HIV Study Group.

The course of pneumonia caused by pyogenic bacteria and Pneumocystis carinii was examined in a multicity cohort study of HIV infection. The median duration of survival among 150 individuals following initial bacterial pneumonia was 24 months, compared with 37 months among 299 human immunodeficiency virus (HIV)-infected control subjects matched by study site and CD4 lymphocyte count (P<.001). For 152 subjects with P. carinii pneumonia, median survival was 23 months, compared with 30 months for 280 matched control subjects (P = .002). Median durations of survival associated with the two types of pneumonia differed by only 47 days, despite a higher median CD4 lymphocyte count associated with bacterial pneumonia. These results suggest that both P. carinii pneumonia and bacterial pneumonia are associated with a significantly worse subsequent HIV disease course. The similarity of prognosis after one episode of bacterial pneumonia vs. an AIDS-defining opportunistic infection and the proportion of cases occurring in association with a CD4 lymphocyte count of >200 suggest that measures to prevent bacterial pneumonia should be emphasized.     

Granulomatous Pneumocystis carinii pneumonia in Wegener's granulomatosis.

This study reports on a first case of granulomatous Pneumocystis carinii pneumonia (PCP) in a human immunodeficiency virus-negative patient with antineutrophil cytoplasmic antibody-positive Wegener's granulomatosis whilst receiving immunosuppressive treatment. The patient presented with diffuse alveolar haemorrhage, pauci-immune rapid progressive glomerulonephritis and leukocytoclastic vasculitis of the skin. Granulomatous Pneumocystis carinii pneumonia developed under immunosuppressive treatment with cyclophosphamide and prednisone. At the time Pneumocystis carinii pneumonia developed, there was a marked lymphopenia with a very low CD8+ cell count in the blood. Grocott staining in bronchoalveolar lavage fluid revealed no Pneumocystis carinii. The diagnosis was made via a video-assisted thoracoscopic lung biopsy which showed granulomas containing high numbers of Pneumocystis carinii cysts.     

Tuberculosis in patients with human immunodeficiency virus infection. How often does it mimic Pneumocystis carinii pneumonia?

Adjunctive corticosteroid therapy is recommended for selected human immunodeficiency virus (HIV)-infected patients with presumed Pneumocystis carinii pneumonia. Because corticosteroids may exacerbate undiagnosed tuberculosis, we evaluated the frequency with which tuberculosis in HIV-infected patients mimics P carinii pneumonia. Over a 12-month period, we identified 105 HIV-infected patients with pleuropulmonary tuberculosis and 84 patients with P carinii pneumonia who were sufficiently hypoxemic to warrant corticosteroid therapy. Of the 105 patients with tuberculosis, acid-fast smears of clinical samples were positive in 49 cases, and chest roentgenographic findings suggested tuberculosis in an additional 44 cases. The 12 patients with negative acid-fast smears and nonspecific chest roentgenographic findings presented a potential diagnostic dilemma between tuberculosis and P carinii pneumonia. Pneumocystis carinii pneumonia should not have been a presumptive diagnosis of eight of these 12 patients because of absence of pulmonary symptoms and chest roentgenographic abnormalities (four cases), a CD4 count greater than 500/cu mm (three cases), or marked lymphadenopathy suggestive of tuberculosis (one case). Thus, only 4 percent (4/105) of HIV-infected patients with pleuropulmonary tuberculosis had clinical and chest roentgenographic features mimicking P carinii pneumonia. Two of these four patients were sufficiently hypoxemic to warrant corticosteroid therapy. Thus, if corticosteroids had been routinely used during the study period, 84 patients with P carinii pneumonia would have been treated, including two patients with undiagnosed tuberculosis. We conclude that the use of corticosteroids for presumed P carinii pneumonia carries a small but acceptable risk of inadvertent exacerbation of tuberculosis, provided clinical and chest roentgenographic features do not suggest tuberculosis.     

Efficacy of trimetrexate, a potent lipid-soluble antifolate, in the treatment of rodent Pneumocystis carinii pneumonia

Trimetrexate is a lipid-soluble antifolate that has been shown in vitro to be a much more potent inhibitor of Pneumocystis carinii dihydrofolate reductase than the conventionally used inhibitor trimethoprim. To evaluate the in vivo efficacy of trimetrexate, steroid-treated rats which spontaneously develop P. carinii pneumonia were used. Rats treated with trimetrexate (25 mg/kg/d) plus sulfamethoxazole (250 mg/kg/d) orally responded at least as well as rats treated with trimethoprim (50 mg/kg/d) plus sulfamethoxazole. Trimetrexate alone administered orally was ineffective in treating P. carinii infection, but subcutaneous (sc) trimetrexate (7 mg/kg/d) significantly decreased the intensity of infection compared to controls. Trimetrexate is a potent antifolate that may provide an effective alternative to pentamidine and trimethoprim-sulfamethoxazole for treatment of P. carinii pneumonia in humans.     

Surfactant phospholipids and lavage phospholipase A2 in experimental Pneumocystis carinii pneumonia

The effect of Pneumocystis carinii pneumonia on surfactant phospholipids and lavage phospholipase A2 was investigated. Pneumocystis carinii infection was induced in adult rats by immunosuppression with dexamethasone administered in the drinking water (2 mg/L) for 6 to 8 wk. Surfactant phospholipids were isolated from lung lavage and lung tissue. Dexamethasone administration significantly increased total lung and lavage phospholipids in corticosteroid-treated animals receiving prophylaxis against P. carinii with trimethoprim-sulfamethoxazole (TMP-SMZ) when compared with no treatment control animals. Lavage surfactant phospholipids from P. carinii-infected rats were 25% that of no treatment control rats and less than 10% that of corticosteroid control animals receiving TMP-SMZ. Phospholipid composition of lavage phospholipids was also altered in P. carinii pneumonia, with slight increase in the percentage of sphingomyelin and reduced percentage of total phosphatidylcholine. Postlavage tissue phospholipids of P. carinii-infected rats were 4 times that of no treatment control animals, although only about 50% that of corticosteroid control animals. There was no significant difference in lavage phospholipase A2 activity for the P. carinii-infected and corticosteroid control groups, although the enzyme activity was at least 4 times that of the no treatment control group. The surfactant changes were associated with abnormal excised lung pressure-volume curves and decreased deflation stability in the animals with P. carinii. These results indicate that the corticosteroids used in this model induce an increase in both lung surfactant phospholipids and phospholipase A2. Despite this increase in lavage phospholipids, P. carinii pneumonia in this model causes an alveolar surfactant phospholipid deficiency without significant increase in phospholipase A2 activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alterations in T lymphocyte profiles of bronchoalveolar lavage fluid from SIV- and Pneumocystis carinii-coinfected rhesus macaques

The goal of this study was to examine SIV- and Pneumocystis carinii-coinfected rhesus macaques as a model of P. carinii infection in HIV-seropositive humans. The influence of P. carinii infection on the cellular composition of bronchoalveolar lavage (BAL) fluid from SIV-infected and normal rhesus macaques was examined by flow cytometric analysis and polymerase chain reaction (PCR). BAL fluid from SIV- and P. carinii coinfected macaques showed a substantial T lymphocyte influx composed of more than 90% CD8+ T cells. These results are in contrast to BAL fluid from SIV-infected macaques with no detectable P. carinii-specific PCR product, where CD4+ T cells were present in significant numbers and the CD8+ T cell population was less than 70% of total CD3+ lymphocytes. We observed no significant differences in peripheral blood CD4+ or CD8+ T cell levels in the SIV-infected animals, regardless of P. carinii status, indicating that the CD8+ T cell infiltration in the lungs of the P. carinii-positive animals was likely the result of P. carinii infection. These results demonstrate that although peripheral blood CD4+ T cell levels are predictive of susceptibility to P. carinii infection in this model, the levels are not reflective of the T cell profile in the lung during SIV and P. carinii coinfection. The SIV- and P. carinii-coinfected macaques showed a spectrum of lung disease severity that was histologically similar to human P. carinii pneumonia (PCP). Interestingly, even mild P. carinii infection was sufficient to alter the normal CD4+/CD8+ T cell profiles in the lungs of SIV-infected rhesus macaques. These results are similar to immunologic findings in human AIDS-associated PCP and support the usefulness of this model in the study of immune responses to P. carinii.     

The role of inflammation in respiratory impairment during Pneumocystis carinii pneumonia

Pneumocystis carinii remains an important cause of pneumonia in immunosuppressed hosts. Severe Pneumocystis pneumonia is characterized by an intense neutrophilic inflammatory response resulting in gas exchange abnormalities, diffuse alveolar damage, and respiratory failure. The inflammatory response directed against P. carinii involves a complex series of interactions between alveolar macrophages, CD4+ T lymphocytes, polymorphonuclear cells, and their various products. CD4+ T lymphocytes are crucial to host defense against P. carinii. Alveolar macrophages also provide essential functions that significantly enhance clearance of P. carinii infection. In addition, host proteins play an important role in augmenting the host inflammatory responses to this organism. Although essential for effective clearance of infection, excessive inflammatory responses also predispose the host to the development of lung injury and respiratory compromise. Understanding the complex processes involved in the host inflammatory response and its potential for causing lung injury may enable development of novel therapeutic approaches for this and other important fungal lung infections.