康乐霉素C对T—和B—淋巴细胞活化的抑制作用

目的：阐明康乐霉素Ｃ对脾细胞增殖和Ｔ－细胞亚型的作用。方法：氚掺入法或噻唑蓝比色法测定细胞增殖；用荧光激活细胞分选仪测定细胞亚群；曲利苯蓝排斥法测定细胞存活率。结果：Ｋａｎ８，４０，８０和４００ｎｍｏｌ．Ｌ＾－１除抑制丝 同种异型抗原刺激的小鼠脾细胞增殖外；与Ｃｉｃ不同，抑制ＬＰＳ刺激的脾细胞增殖；使Ｌ３Ｔ４＾｜Ｌ－细胞亚型比倒置；     

康乐霉素C还原酶的初步研究

利用康乐霉素 C(简称 K- C)产生菌地中海诺卡氏菌康乐变种 U1 5- S- 1建立了产酶的发酵培养基和工艺条件 ,确定了康乐霉素 C在发酵过程中产生还原酶系 ,可以还原 SF2 315 A成为康乐霉素 C,且阻遏了康乐霉素 C的氧化 ,而且证明其为胞内酶     

康乐霉素C产生菌的诱变育种及其发酵的研究

康乐霉素Ｃ（简称Ｋ－Ｃ）是一个新的免疫抑制剂,但它在发酵液中含量很低,仅为０．１ｍｌ／Ｌ。为了满足药效学、毒理学试验和药代动力学所需的样品,就必须提高Ｋ－Ｃ的产量。Ｋ－Ｃ的产生菌为Ｎｏｃａｒｄｉａ ｍｅｄｉｔｅｒｒａｎｅｉ ｖａｒ．Ｋａｎｇｌｅｎｓｉｓ １７４７－６４,用本所的自然突变株ＳＴ－９１为出发菌株（下称出发菌株）,采用紫外线诱变和自然分离纯化的方法,筛选出１株Ｋ－Ｃ的产量明显地高于出发菌     

新免疫抑制剂—康乐霉素C的发酵,分离,理化性质和生物学…

从我所提供的Ｎｏｃａｒｄｉａ ｍｅｄｉｔｅｒｒａｎｅｉ ｖａｒ．ｋａｎｇｌｅｎｓｉｓ１７６７－６４已分离出了３种确定了经构的新抗生素，即康乐霉素Ａ、康乐霉素Ｃ和３１－ｈｏｍｏｒｉｆａｍｙｃｉｎ Ｗ。由于康乐霉素Ｃ具有很强的免疫抑制作用，在体外其活性如环孢菌素Ａ，具有很好的抗肿瘤活性。本文报道康乐霉素Ｃ的发酵、分离、理化性质和生物学性质。     

康乐霉素C的结构测定

新抗生素康乐霉素Ｃ已从Ｎｏｃａｒｄｉａｍｅｄｉｔｅｒｒａｎｅｉｖａｒ．ｋａｎｇｌｅｎｓｉｓ１７４７－６４的发酵液中分离出来。它对革兰氏阳性菌有弱抗菌活性，但具有很强的免疫抑制作用。康乐霉紊Ｃ具有苯骄［ａ］惠的碳架，本文根据光谱分析和单晶Ｘ－衍射分析来阐明康乐霉素Ｃ的结构，确定为：［４ａＲ，６ａＲ，１２ａＲ，１２ｂＳ］ｏｒ［４ａＳ，６ａＳ，１２ａＳ，１２ｂＲ］－４ａ，５，６，６ａ，１２ａ，１２ｂｈｅｘａｈｙｄｒｏ－４ａ，８－ｄｉｈｙｄｒｏｘｙ－３ｍｅｔｈｙｌｂｅｎｚ（ａ）ａｎｔｈｒａｃｅｎ－１，７，１２（４Ｈ）－ｔｒｉｏｎｅ．     

康乐霉素C对T-和B-淋巴细胞活化的抑制作用(英文)

阐明康乐霉素Ｃ（Ｋａｎ）对脾细胞增殖和Ｔ－细胞亚型的作用。方法：氚掺入法或噻唑蓝（ＭＴＴ）比色法测定细胞增殖;用荧光激活细胞分选仪（ＦＡＣＳ）测定细胞亚型;曲利苯蓝排斥法测定细胞存活率．结果： Ｋａｎ ８, ４０, ８０和 ４００ ｎｍｏｌ· Ｌ－１,除抑制丝裂原（Ｃｏｎ Ａ, ＰＨＡ和 ＴＰＡ＋ＩＭ）和同种异型抗原刺激的小鼠脾细胞增殖外;与Ｃｉｃ不同,抑制ＬＰＳ （１０ｍｇ·Ｌ－１）刺激的脾细胞增殖;使Ｌ３Ｔ４＋／Ｌｙｔ２＋ Ｔ－细胞亚型比值倒置; Ｋａｎ于 Ｃｏｎ Ａ（ ５ｍｇ· Ｌ－１）刺激后 ２４ ｈ内加入,仍抑制脾细胞增殖． Ｋａｎ Ｂ－４００ ｎｍｏｌ· Ｌ－１不影响脾细胞存活率。结论：与Ｃｉｃ的作用方式不同,Ｋａｎ抑制Ｔ－和Ｂ－细胞活化的早期和晚期时相,抑制细胞增殖,对Ｔｎ－细胞有选择性。     

康乐霉素C的稳定性及其提炼工艺改进

阿乐霉素C是从地中海诺卡氏菌康乐变种1747－64中分离得到的一个免疫抑制剂,其结构中的C6a-C12a键在使用硅胶柱层析的提取纯化过程中易氧化。改用HP－20树脂进行分离纯化,可明显降低氧化,且康乐霉素C在HP－20柱后收率大于80％。     

新苯骈蒽醌类抗生素康乐霉素M的分离和结构测定

从Ｎｏｃａｒｄｉａｍｅｄｉｔｅｒｒａｎｅｉｖａｒ．ｋａｎｇｌｅｎｓｉｓ１７４７－６４的发酵液中分离到１个新的苯骈蒽醌类抗生素康乐霉素Ｍ。它对革兰氏阳性菌有一定的抑制作用。基于质谱和核磁共振氢谱分析，以及与已知苯骈蒽醌类抗生素的比较，阐明其结构为１，８－ｄｉｈｙｄｒｏｘｙ－３－ｈｙｄｒｏｘｙｍｅｔｈｙｌ－Ｂｅｎｚ［ａ］ａｎｔｈｒａｃｅｎｅ－７，１２－ｄｉｏｎｅ。     

康乐霉素产生菌—地中海诺卡氏菌康乐变种的分类鉴定

康乐霉素属于利福霉素族，其Ａ成份是一种新抗生素。康乐霉素产生菌１７４７－６４是从广州康乐县土壤中分离出来的，根据分类研究，菌株应归属于诺卡氏菌，是地中海诺卡氏菌的一新变种，定名为地中海诺卡氏菌康乐变种１７４７－６４。     

Kanglemycin C vs ciclosporin on immunosuppression in mice

目的：与环孢素（Ｃｉｃ）比较,研究康乐霉素Ｃ（Ｋａｎ）对小鼠免疫系统的影响．方法：皮肤迟发性超敏反应（ＤＨ）和环磷酰胺（Ｃｙｃ）增强型ＤＨ;同种异型皮肤和心脏移植;脾细胞溶血素测定;腹腔巨噬细胞吞噬中性红．结果：Ｋａｎ（１２５,２５,５０ｍｇ·ｋｇ－１·ｄ－１,ｉｇ,８ｄ）与Ｃｉｃ相似,抑制小鼠皮肤ＤＨ和Ｃｙｃ增强型ＤＨ（Ｐ＜００１）;延长小鼠同种异型皮肤和心脏移植物存活时间（Ｐ＜００１）;对溶血素产生也有抑制作用（Ｐ＜００１）;Ｋａｎ５０ｍｇ·ｋｇ－１·ｄ－１,ｉｇ,５ｄ与Ｃｙｃ相似,对小鼠腹腔巨噬细胞吞噬中性红无明显作用（Ｐ＞００５）．结论：Ｋａｎ显著抑制小鼠细胞免疫和体液免疫,但不影响巨噬细胞的吞噬．     

环孢素纳米脂质体的制备及在小鼠体内的组织分布

目的 :研究小鼠灌胃给予环孢素纳米脂质体后药物在主要脏器中的分布。方法 :利用旋转薄膜 超声法制备环孢素纳米脂质体、考察其形态、含量、包封率、粒径、多分散指数及Zeta电位。并以环孢素微乳软胶囊内容物为对照 ,小鼠灌胃给药 ,考察环孢素在全血及心、肝、脾、肺、肾、皮肤的分布特征。结果 :环孢素纳米脂质体均匀圆整 ,含量为 (3.14±s0 .0 6 ) g·L- 1,包封率为 (98.91± 0 .0 8) % ,粒径(6 4± 5 )nm ,多分散指数为 (43± 6 ) % ,Zeta电位为 13mv。给予环孢素纳米脂质体后药物在全血及各组织的AUC0 2 4 低于环孢素微乳软胶囊内容物的AUC0 2 4 ,而MRT值则较大。结论 :环孢素纳米脂质体未能进一步促进环孢素的吸收 ,但在一定程度上改变了它的体内分布 ,延长了MRT     

新鲜与陈旧 霉素诱导小鼠体内非1gE抗体应答的对比

AIM: To study whether or not the freshly prepared benzylpenicillin could induce different non-IgE antibody response from aged benzylpenicillin. METHODS: Antibody response was determined by enzyme-linked immunosorbent assay (ELISA). Antigen molecules recognized by antibodies and antigenic cross reactions were tested by hapten inhibition assay. RESULTS: Isotypes of specific non-IgE antibodies induced by freshly prepared benzylpenicillin were mainly IgM, and then IgG and IgA. Some parts of specific antibodies recognized benzylpenicillin molecule and major parts combined with degraded or transforming products. Isotypes of antibodies responsible for cross reaction were mainly IgG between benzylpenicillin and ampicillin and IgM between benzylpenicillin and piperacillin. CONCLUSION: Freshly prepared and aged benzylpenicillin induced different non-IgE antibody response.     

Modeling and predicting stress-induced immunosuppression in mice using blood parameters.

Previous studies have shown that the area under the corticosterone concentration vs. time curve (AUC) can be used to model and predict the effects of restraint stress and chemical stressors on a variety of immunological parameters in the mouse spleen and thymus. In order to complete a risk assessment parallelogram, similar data are needed with blood as the source of immune system cells, because this is the only tissue routinely available from human subjects. Therefore, studies were conducted using treatments for which the corticosterone AUC values are already known: exogenous corticosterone, restraint, propanil, atrazine, and ethanol. Immunological parameters were measured using peripheral blood from mice treated with a series of dosages of each of these agents. Flow cytometry was used to quantify MHC II, B220, CD4, and CD8 cells. Leukocyte and differential counts were done. Spleen cell number and NK cell activity were evaluated to confirm similarity to previous studies. Immune parameter data from mouse blood indicate that MHC II expression has consistent quantitative relationships to corticosterone AUC values, similar to but less consistent than those observed in the spleen. Other immune parameters tended to have greater variability in the blood than in the spleen. The pattern observed in the spleen in which the chemical stressors generally produced very similar effects as noted for restraint stress (at the same corticosterone AUC values) was not observed for blood leukocytes. Nevertheless, MHC class II expression seems to provide a reasonably consistent indication of stress exposure in blood and spleen.     

复方HD对环磷酰胺致免疫抑制小鼠免疫功能的影响

目的 探讨复方HD对环磷酰胺诱导的免疫抑制小鼠的免疫增强作用。方法 ICR小鼠分别以蒸馏水（对照组、模型组）、香菇多糖（200 mg/kg）、复方HD（5、10、20 g/kg）每天1次ig给药,连续10 d;除对照组外,在第4~6天ip环磷酰胺（40 mg/kg）制备免疫抑制小鼠模型（对照组除外）;每天给药前精确称量并记录小鼠体质量。于最后一次给药24 h后,测定小鼠脾指数、胸腺指数;流式细胞术进行全血中T细胞亚群分析;ELISA法检测血浆中IFN-γ和IL-4水平。结果 与模型组比较,复方HD低、中、高剂量组显著提高小鼠的胸腺指数,CD3⁺、CD3⁺CD4⁺细胞数以及CD4⁺/CD8⁺比值（P<0.05）,显著恢复血浆中IFN-γ水平和IFN-γ/IL-4比值（P<0.05）,纠正了Th1/Th2偏移,并呈现出一定的浓度相关性。结论 复方HD能够促进环磷酰胺诱导的免疫抑制小鼠免疫功能的恢复,证明其在预防及治疗免疫功能低下方面具有一定的疗效。     

Time limitations in the reversal by citrovorum factor of methotrexate-induced immunosuppression in mice.

Methotrexate was found to inhibit both the complement-dependent and the complement-independent cellular cytotoxicity of spleen cells from mice immunized with sheep erythrocytes. The inhibition was essentially complete when a single dose of 100 mg/kg (about one-half the ld₅₀) was given 2 days after antigen administration, and the response was measured on day 4. Recovery from this inhibition was incomplete on days 5–7 and complete on day 14. The inhibition measured on day 4 could be partially prevented by citrovorum factor (200 mg/kg), but only if this compound was administered 1–5 hr before methotrexate. In contrast, the residual inhibition measured during recovery, on day 7, was completely reversed if citrovorum factor was injected even as late as 6 hr after methotrexate on day 2. The data suggest that protection of the majority of the rapidly proliferating, antigen-stimulated, spleen lymphoid cells from the effects of methotrexate can be provided only by preloading these cells with citrovorum factor.     

原花青素对环磷酰胺致免疫抑制小鼠免疫功能的影响

目的 探究原花青素（PC）对环磷酰胺（Cy）致免疫抑制小鼠的免疫调节作用及其对白细胞介素-10（IL-10）、肿瘤坏死因子-α（TNF-α）表达的影响。方法 选用40只ICR小鼠,随机均分为正常对照组、Cy模型组、PC高剂量组（100 mg/kg）和PC低剂量组（80 mg/kg）。灌胃给药,7 d后测定各组小鼠胸腺（脾脏）指数、血清溶血素水平、迟发型超敏反应性;酶联免疫吸附测定（ELISA）检测外周血IL-10和TNF-α的表达;RT-qPCR测定小鼠脾脏TNF-α和IL-10 mRNA的表达。结果 PC能够提高小鼠胸腺、脾脏指数,一定程度恢复免疫抑制小鼠的迟发型超敏反应能力,提高血清溶血素含量;同时PC也可降低外周血IL-10的表达,升高TNF-α的表达;降低脾细胞IL-10 mRNA的水平,升高TNF-α mRNA的水平。结论 原花青素可以提升机体免疫功能,其调节机制可能是通过对细胞因子TNF-α和IL-10的调节来完成的。