地塞米松、谷氨酰胺对内毒素血症大鼠心肌TNF-α的影响

Effects of dexamethosone, glutamine on myocardial TNF-αof rats with endotoxemia

目的通过观察地塞米松、谷氨酰胺对内毒素血症大鼠心肌TNF-α的影响,探讨地塞米松、谷氨酰胺对内毒素血症大鼠心肌的保护途径。方法选健康18日龄Wistar大鼠248只,随机取8只腹腔注射生理盐水作对照组(0h),其余大鼠按腹腔注射药物不同分成内毒素(L)、地塞米松预防(Dex)、谷氨酰胺预防(Gln)地塞米松治疗(D1)及混合I(GD)混合II(GD1)组,每组40只,各组于加LPS后2、4、6、24及72h分别断头取心脏固定,石蜡切片,用免疫组化方法测定TNF-α。结果L组心肌TNF-α在2、24h出现两次升高,、后者升高程度更明显,差异显著,P<0.01;Dex、Gln、D1、GD和GD1组均出现心肌TNF-α升高减弱或后移现象,而且后者抑制作用更强,差异显著,P<0.01,其中抑制作用最强的组为GD1组。结论TNF-α在内毒素血症心肌中起一定的损害作用,地塞米松对TNF-α的合成有抑制作用,这种作用在推后1h给予效果更明显;谷氨酰胺对TNF-α的合成也有抑制作用,在使第一个高峰后移的同时各个时间点TNF-α峰值均降低;二者有协同作用。

[Objective] To observe effects of dexamethosone, glutamine on myocardial TNF alpha of rats with endotoxemia. [Methods] Wistar rat endotoxemia model was established first by injection of a dose of LPS （4 mg/kg, Escherichia coli O111：B4 ） in 18-day-rat via abdominal cavity, then sacrificed after 0, 2, 4, 6, 24 and 72 h, respectively, the hearts were isolated from the rats whose were injected salt/LPS＋Dex/LPS＋Gln/LPS＋Gln＋Dex/ LPS＋1 h late Dex/LPS＋Gln＋1 h late Dex respectively. The isolated hearts were fixed in order to measure the levels of TNF-α with immunohis to chemitry. [Results] In rats with LPS, TNF-α increased to first peak at 2 h, and then gradually descended, by 24 h, the level of TNF-α rose again to the second peak. The Integrated OD Total of TNF- alpha were （14550±1495）, （120482±5192）, （79110±3536）, （62643±3904）, （134793±6623）, （76077±2915）, respectively at different concentration points, there was significant difference between＇the two groups （P 〈0.01）; in Dex or Gin groups, TNF-α were lower than LPS group and higher than in GD group, there was significant difference between the two groups （P 〈0.01）, while the TNF-α depressions are more significant in D1 and in GD1 group than in Dex and Gin groups, P 〈0.01. [Conclusion] TNF-α plays an important role in the activation of LPS-induced endotoxemia. It can result myocardic damage, While dexamethesone and glutamine can protect the heart by decrease TNF-α, if combine with them, the depressing were more significant; if give dexamethesone 1 hour later, the depressing were more significant.