PARTIAL CHARACTERIZATION OF THE ENHANCED SURVIVAL OF FEMALE NZB/W MICE TREATED WITH LITHIUM-CHLORIDE
PARTIAL CHARACTERIZATION OF THE ENHANCED SURVIVAL OF FEMALE NZB/W MICE TREATED WITH LITHIUM-CHLORIDE
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DOI：
10.1016/0192-0561(94)90056-6
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发表时间：
1994-10-01
期刊：
影响因子：
--
通讯作者：
LENZ, SP
中科院分区：
文献类型：
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作者：
HART, DA;DONE, SJ;LENZ, SP
以前的研究表明，10周龄的雌性NZB/W小鼠开始接受LiCl治疗(每天4 mg)，可以提高50%的小鼠到11个月龄的存活率(Lithium，3，61-67,1992)。目前的结果表明，这种提高存活率的作用是剂量依赖性的，因为每天2 mg(LiCl)-Li-7的效果不如4 mg(LiCl)-Li-7/天。从8周龄开始，每天服用2 mg或4 mg LiCl组的小鼠在40周龄时的存活率分别为40%和70%，而同期只有10%的未处理组小鼠存活。在病程明显(24周龄)后开始每天服用2毫克(LiCl)-Li-7治疗会导致疗效降低。对每天服用4 mg(LiCl)-Li-7的小鼠的平行实验显示，早期治疗组和延迟治疗组的长期存活率分别为60%和33%。两组停止治疗导致了一些额外的死亡，但20-27%的小鼠在60周大时仍然存活，尽管动物的血清中检测到了抗单链DNA抗体的水平。在NZB/W小鼠中，每天用2和4 mg(LiCl)-Li-7进行额外的实验，这种治疗方法以前被证明可以提高存活率(Int.J.免疫学杂志，14，35-41,1992)，表明这两种方式的效果不是相加的。这些结果表明，用LiCl2处理NZB/W小鼠可以通过独特的机制非常有效地延长存活时间，可能涉及改变肾脏自身免疫损伤的效应阶段或肾脏元素对导致肾功能衰竭的免疫介导性损伤的易感性。
Previous investigations have indicated that initiation of LiCl treatment (4 mg/day) of female NZB/W mice at 10 weeks of age led to enhanced survival of 50% of the mice to >11 months of age (Lithium, 3, 61-67, 1992). The present results indicate that this enhancement of survival is dose dependent in that 2 mg (LiCl)-Li-7/day was less effective than 4 mg (LiCl)-Li-7/day. Daily treatment of groups of mice with 2 or 4 mg LiCl per day starting at 8 weeks of age led to the survival of 40% and 70%, respectively, of the mice at 40 weeks of age, a time when only 10% of the untreated mice remained alive. Initiation of treatment with 2 mg (LiCl)-Li-7/day after the disease process was evident (24 weeks of age) led to diminished effectiveness. Parallel experiments with mice treated with 4 mg (LiCl)-Li-7/day revealed 60% long-term survivors in the early treatment groups and 33% in the delayed treatment groups. Cessation of treatment in both groups led to some additional deaths, but 20-27% of the mice remained alive at 60 weeks of age, even though animals had detectable levels of anti-ssDNA antibodies in their serum. Additional experiments with 2 and 4 mg (LiCl)-Li-7/day in NZB/W mice pretreated with C. parvum-PER, a treatment previously shown to enhance survival (Int. J. Immunopharmac., 14, 35-41, 1992), indicated that the effect of the two modalities was not additive. The results presented indicate that treatment of NZB/W mice with LiCl leads to very effective prolongation of survival by unique mechanisms, possibly involving alteration of the effector phase of autoimmune damage to the kidney or the susceptibility of kidney elements to immune-mediated damage leading to renal failure.