摘要
目的探讨甘草酸18α体对肾脏缺血再灌注损伤(ischemia reperfusion injury,IRI)后肾小管上皮细胞p53蛋白表达的影响及其意义。方法将成年(2月龄)野生型鼠[p53(+/+)]和p53基因敲除[p53(-/-)]鼠分成4组:p53(+/+)鼠生理盐水组、p53(+/+)鼠甘草酸治疗组、p53(-/-)鼠生理盐水组和p53(-/-)鼠甘草酸治疗组;建立左肾IRI模型,于再灌注后0、1和7d处死动物,制作双肾(右肾作自身对照)标本。HE染色观察肾组织病理变化,免疫组化法检测NF-κB蛋白的表达,Western blot定量检测p53的表达,并用EIG综合图像分析系统对NF-κB的表达进行半定量分析。结果缺血再灌注损伤肾脏主要表现为肾小管坏死,半定量分析结果显示甘草酸治疗组比生理盐水组轻、p53(+/+)鼠组比p53(-/-)鼠组轻(P<0.01)。各组IRI肾NF-κB蛋白的表达在IRI后0d即开始增加,1、7d点,NF-κB蛋白的表达在p53(+/+)鼠比p53(-/-)鼠显著减少,甘草酸治疗组比生理盐水组显著减少(P<0.01);p53(+/+)鼠甘草酸治疗组p53蛋白的表达比生理盐水组显著增多(P<0.01)。p53的表达与肾小管坏死和NF-κB的表达呈显著负相关(P<0.01)。结论甘草酸可能主要通过对小鼠IRI肾脏p53表达的上调,抑制NF-κB的表达,减轻肾小管坏死,从而对IRI肾脏产生保护作用。
Objective To investigate the effect of glycyrrhizin-18α on the expression of p53 in renal tubular epithelial cells after renal ischemia-reperfusion injury （IRI）. Methods p53 （ ＋/＋ ） and p53 （-/-） male mice aged 2 months were used to make ischemic model by clamping left renal hila for 45 rain, then immediately and on each following day, the animals were treated with glycyrrhizin-18α （20 mg·kg^-1·d^-1 ） or normal sodium （control） by subcutaneous injection. On day 0, 1 and 7 after reperfusion, renal tissues were processed for morphometric observation as well as NF-κB and p53 proteins analysis, using HE stain, immunohistoehemistry and Western blot, respectively. Results In the IRI kidney, renal tubular necrosis was more severe in p53 （-/-） mice and normal sodium treated mice than in p53（ ＋/＋ ） mice and glycyrrhizin-18α treated mice （P 〈 0.01 ） , respectively. The expressions of p53 and NF-κB proteins began to increase on day 0 after IRI, but the expression of NF-KB protein began to decrease on day 1 to 7, while the expression of p53 protein was still at a high level. The expression of p53 protein in p53 （ ＋/＋ ） mice treated with glycyrrhizin-18α increased obviously compared with that in p53（ ＋/＋ ） mice treated with normal sodium （P 〈0.01 ）, but the expression of NF-κB protein decreased obviously （P 〈0. 01 ）. The expression of p53 protein was negatively correlated with renal tubular necrosis and the expressions of NF-κB protein （P 〈0.01 ）. Conclusion Glycyrrhizin-18α may inhibit the expression of NF-κB protein by upregulating the expression of p53 protein, resulting in relieving renal tubular necrosis.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2008年第22期2078-2081,共4页
Journal of Third Military Medical University
基金
"长江学者奖励计划"特聘教授配套经费~~
