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各种药物对胰岛素抗体的影响。

Effects of various drugs on insulin antibodies.

作者信息

Gulati O D, Patel D G

出版信息

Br J Pharmacol. 1971 May;42(1):66-77. doi: 10.1111/j.1476-5381.1971.tb07087.x.

Abstract
  1. Insulin antibodies were induced in young guinea-pigs of both sexes weighing 300-400 g and housed in a room maintained at 28 degrees C+/-2 degrees C, by subcutaneous injection of 2 ml of freshly prepared insulin antigen emulsion between the shoulders once every month.2. To estimate the titre of serum antibody the serum was incubated with a known concentration of insulin for 90 min at 37 degrees C and the insulin not bound to antibody was estimated by the rat hemidiaphragm method.3. No significant (P>0.5) development of insulin antibody could be detected in the serum samples collected 1 month after the first and 15 days after the second monthly injections in groups of ten male guinea-pigs and six female guinea-pigs. However, the titre of insulin antibody in the serum of these groups of guinea-pigs 15 days after the third monthly injection of insulin antigen emulsion was significantly (P<0.01) raised. There was no further increase in the titre of insulin antibody in the sera 15 days after the fourth and fifth monthly injections of insulin antigen emulsion. Thus the peak titre was reached 15 days after the third monthly injection of the antigen.4. Two groups of ten male guinea-pigs each received testosterone propionate or diethylstilboestrol daily for 1 week after each monthly injection of insulin antigen emulsion. Two other groups of six female guinea-pigs each received testosterone propionate or diethylstilboestrol in a similar manner. One more group of ten female guinea-pigs received both sex hormones for 1 week after each monthly injection of insulin antigen emulsion. Testosterone facilitated the induction of insulin antibody in the serum of males but did not affect the antibody titre in the female guinea-pigs. Diethylstilboestrol facilitated the induction of insulin antibody in the serum of groups of either sex, the peak titre being attained after the second monthly injection of insulin antigen emulsion. The response of the females which received both sex hormones was similar to that of females which received diethylstilboestrol alone.5. Fifteen days after the third monthly injection of insulin antigen emulsion a group of ten guinea-pigs received hydrocortisone subcutaneously each day for 1 month. The serum antibody titre was estimated at the end of the drug treatment, and was significantly (P<0.01) reduced.6. Fifteen days after the third monthly injection of insulin antigen emulsion three different groups of five-six guinea-pigs each received tolbutamide, chlorpropamide or phenformin orally every day for a month. Antibody titres of the serum were estimated at the end of this period; there was no significant (P>0.05) reduction in groups receiving chlorpropamide or phenformin, but the serum antibody titre of the group receiving tolbutamide was significantly (P<0.01) raised.7. Fifteen days after the third monthly injection of insulin antigen emulsion different groups of five-six guinea-pigs received one of the following: 5-bromouracil, 5-fluorouracil, 6-mercaptopurine, methotrexate, 6-azauridine, busulphan, chlorambucil, cyclophosphamide, actinomycin-D or mytomycin-C intraperitoneally each day for 5 days. The serum antibody titre of all the groups of guinea-pigs was significantly (P<0.01) reduced. On the other hand the serum antibody titre of a control group of six guinea-pigs receiving normal saline intraperitoneally each day for 5 days was not significantly (P>0.5) affected.
摘要
  1. 对体重300 - 400克、饲养在温度保持在28摄氏度±2摄氏度房间内的雌雄幼年豚鼠,通过每月在肩部皮下注射2毫升新制备的胰岛素抗原乳剂来诱导胰岛素抗体。

  2. 为了估计血清抗体滴度,将血清与已知浓度的胰岛素在37摄氏度下孵育90分钟,未与抗体结合的胰岛素通过大鼠半膈肌法进行测定。

  3. 在10只雄性豚鼠和6只雌性豚鼠组中,首次注射后1个月以及第二次每月注射后15天采集的血清样本中,未检测到胰岛素抗体有显著(P>0.5)的产生。然而,在第三次每月注射胰岛素抗原乳剂后15天,这些豚鼠组血清中的胰岛素抗体滴度显著(P<0.01)升高。在第四次和第五次每月注射胰岛素抗原乳剂后15天,血清中胰岛素抗体滴度没有进一步增加。因此,在第三次每月注射抗原后15天达到峰值滴度。

  4. 在每次每月注射胰岛素抗原乳剂后,两组各10只雄性豚鼠每天接受丙酸睾酮或己烯雌酚注射,持续1周。另外两组各6只雌性豚鼠也以类似方式接受丙酸睾酮或己烯雌酚注射。还有一组10只雌性豚鼠在每次每月注射胰岛素抗原乳剂后接受两种性激素注射,持续1周。睾酮促进了雄性血清中胰岛素抗体诱导,但对雌性豚鼠的抗体滴度没有影响。己烯雌酚促进了两性组血清中胰岛素抗体诱导,在第二次每月注射胰岛素抗原乳剂后达到峰值滴度。接受两种性激素的雌性的反应与仅接受己烯雌酚的雌性相似。

  5. 在第三次每月注射胰岛素抗原乳剂后15天,一组10只豚鼠每天皮下注射氢化可的松,持续1个月。在药物治疗结束时估计血清抗体滴度,显著(P<0.01)降低。

  6. 在第三次每月注射胰岛素抗原乳剂后15天,三组各5 - 6只豚鼠每天分别口服甲苯磺丁脲、氯磺丙脲或苯乙双胍,持续1个月。在此期间结束时估计血清抗体滴度;接受氯磺丙脲或苯乙双胍的组没有显著(P>0.05)降低,但接受甲苯磺丁脲的组血清抗体滴度显著(P<0.01)升高。

  7. 在第三次每月注射胰岛素抗原乳剂后15天,不同组的5 - 6只豚鼠每天腹腔注射以下药物之一:5 - 溴尿嘧啶、5 - 氟尿嘧啶、6 - 巯基嘌呤、甲氨蝶呤、6 - 氮尿苷、白消安、苯丁酸氮芥、环磷酰胺、放线菌素 - D或丝裂霉素 - C持续5天。所有豚鼠组的血清抗体滴度显著(P<0.01)降低。另一方面,每天腹腔注射生理盐水持续5天的6只豚鼠对照组的血清抗体滴度没有显著(P>0.5)受到影响。

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本文引用的文献

1
Plasma insulin in human diabetes mellitus.人类糖尿病中的血浆胰岛素
Br Med J. 1951 Dec 29;2(4747):1541-4. doi: 10.1136/bmj.2.4747.1541.
5
Immunologic aspects of insulin.胰岛素的免疫学方面
Am J Med. 1961 Dec;31:882-91. doi: 10.1016/0002-9343(61)90030-4.
7
Insulin antibodies.胰岛素抗体
Lancet. 1963 Aug 3;2(7301):221-2. doi: 10.1016/s0140-6736(63)90117-x.
8
Effect of diethylstilboestrol on the serum gamma-globulin in the guinea pig.
Nature. 1961 Nov 11;192:565-6. doi: 10.1038/192565a0.

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