Indomethacin reverses decreased hippocampal cell proliferation in streptozotocin-induced diabetic mice.
Indomethacin reverses decreased hippocampal cell proliferation in streptozotocin-induced diabetic mice.
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DOI：
10.1007/s11011-014-9611-7
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发表时间：
2015-04
影响因子：
3.6
通讯作者：
Lucki I
中科院分区：
文献类型：
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作者：
Ho N;Brookshire BR;Clark JE;Lucki I
人类和动物的糖尿病伴有慢性低度炎症，这可能是发展神经病理学和神经行为缺陷的可能介质。本研究的目的是确定减少炎症是否可以逆转糖尿病诱导的海马细胞增殖减少，海马神经发生的一个方面。通过施用链脲佐菌素（STZ; 195 mg/kg）使C57 BL/6 J小鼠患糖尿病。STZ小鼠或载体对照接受非甾体抗炎药吲哚美辛的长期治疗（2 mg/kg，持续14天）。测定血浆中的葡萄糖、皮质酮和细胞因子水平，采用BrdU掺入法测定海马中的细胞增殖，采用实时PCR法测定TNF-αR1和TNF-αR2 mRNA。STZ诱导的糖尿病增加了血糖和皮质酮的血浆水平，并降低了体重。糖尿病小鼠海马区的细胞增殖减少了50%。吲哚美辛长期治疗可逆转细胞增殖水平的下降，而皮质酮和葡萄糖水平无变化。糖尿病小鼠血浆TNF-α水平升高，并通过吲哚美辛治疗恢复正常，IL-1和IL-6水平未受糖尿病或吲哚美辛影响。相比之下，糖尿病小鼠的细胞因子IL-10和IFN-γ的血浆水平降低，并且不受吲哚美辛治疗的影响。STZ诱导的糖尿病降低TNF-αR2 mRNA的表达，但不影响TNF-αR1 mRNA的表达。吲哚美辛可能通过介导促炎细胞因子TNF-α而改善STZ对海马神经发生的作用，而不依赖于皮质酮和血糖控制。炎症是一个潜在的新的药理学靶点，用于减轻糖尿病引起的神经行为并发症。
Diabetes in humans and animals is accompanied by chronic low-grade inflammation, which could be a possible mediator of developing neuropathology and neurobehavioral deficits. The objective of the present study determined if decreasing inflammation could reverse diabetes-induced decreases in hippocampal cell proliferation, one aspect of hippocampal neurogenesis. C57BL/6J mice were made diabetic by administering streptozotocin (STZ; 195 mg/kg). STZ mice or vehicle controls received chronic treatment with the non-steroidal anti-inflammatory drug indomethacin (2 mg/kg for 14 days). Levels of glucose, corticosterone and, cytokines were measured from plasma, cell proliferation was measured using BrdU incorporation in the hippocampus and TNF-αR1 and TNF-αR2 mRNA was measured using real-time PCR. STZ-induced diabetes increased plasma levels of glucose and corticosterone and decreased body weight. Cell proliferation in the hippocampus was reduced in diabetic mice by 50%. The decreased level of cell proliferation was reversed by chronic treatment with indomethacin without changes to corticosterone and glucose levels. Plasma TNF-α levels increased in diabetic mice and were normalized by indomethacin treatment and IL-1 and IL-6 levels were unchanged by diabetes or indomethacin. In contrast, plasma levels of the cytokines IL-10 and IFN-gamma decreased in diabetic mice and were not affected by indomethacin treatment. STZ-induced diabetes decreased expression of TNF-αR2 but not TNF-αR1 mRNA. Indomethacin ameliorated the effects of STZ on hippocampal neurogenesis independent of corticosterone and glycemic control, possibly by mediating the proinflammatory cytokine TNF-α. Inflammation is a potential novel pharmacological target for alleviating neurobehavioral complications arising from diabetes.
影响因子：
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作者：
Cho WC;Yip TT;Chung WS;Leung AW;Cheng CH;Yue KK
通讯作者：
Yue KK