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[早期补充维生素D对大鼠哮喘模型中白细胞介素-10和细胞间黏附分子-1表达的影响]

[Effect of vitamin D supplementation in early life on the expression of interleukin-10 and intercellular adhesion molecule-1 in rat asthma model].

作者信息

Zhang Qiao-ling, Zhou Xiao-jian, Hong Jian-guo

机构信息

Department of Pediatrics, Shanghai No.1 People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200080, China.

出版信息

Zhonghua Er Ke Za Zhi. 2009 Oct;47(10):735-9.

Abstract

OBJECTIVE

To explore the effect and mechanism of vitamin D supplementation in early life on rat asthma model.

METHOD

Thirty two sex-mature, female Wistar rats were randomly divided into a control group (n = 8), a low dose group (n = 8), a medium dose group (n = 8) and a high dose group (n = 8). From the seventh day of pregnancy on, the rats in each group were given different doses of vitamin D by intragastric administration, until the offspring rats were 21 days old. The rats in the control group were fed with DMSO-PBS. After the offsprings were weaned, 8 rats were randomly selected from each group. The number of male and female rats was equal. The rats were sensitized to ovalbumin (OVA) and challenged with aerosol OVA to establish the asthma model. The lung tissues were examined for pathologic changes after HE staining. ELISA was used to determine the concentrations of IL-10 in serum and BALF. Immunohistochemical staining methods were used to measure the expression of intercellular adhesion molecule-1 (ICAM-1) in lung tissues.

RESULT

(1) Pathologic changes of lung tissues: compared with the control group, light microscope (LM) showed that eosinophil cells infiltration and the airway inflammation decreased in the low dose and medium dose groups, but increased in the high dose group. (2) The concentrations of IL-10 in serum and BALF: In serum, compared with the control group [(18.7 +/- 4.7) pg/ml], the concentrations of IL-10 in the low dose group [(30.2 +/- 2.8) pg/ml, P < 0.05] and the medium dose group [(51.5 +/- 6.6) pg/ml, P < 0.05] were significantly increased. And the IL-10 level of medium dose group was higher than that of the low dose group (P < 0.05). In BALF, compared with the control group [(59.1 +/- 14.4) pg/ml], the concentrations of IL-10 in the medium dose group [(90.0 +/- 14.3) pg/ml, P < 0.05] was significantly increased. There were no significant changes in the low dose group [(58.1 +/- 3.4) pg/ml, P > 0.05], whereas in the high dose group [(45.3 +/- 6.5) pg/ml, P < 0.05] the level significantly decreased. (2) The expression of ICAM-1 in lung tissues: compared with the control group, there were no significant changes in the low dose group (P > 0.05). The expression of ICAM-1 was significantly decreased in the medium dose group (P < 0.05). In the high dose group, the expression of ICAM-1 was significantly increased (P > 0.05).

CONCLUSION

Adequate intervention with 1,25(OH)2D3 in the early life could alleviate the inflammation in the lung tissues, reduces eosinophil cell infiltration in rat asthma model. However, overdose might play a detrimental role. Its mechanism may be associated with the effect of 1,25(OH)2D3 on IL-10 secretion and the expression of ICAM-1.

摘要

目的

探讨生命早期补充维生素D对大鼠哮喘模型的影响及机制。

方法

将32只性成熟雌性Wistar大鼠随机分为对照组(n = 8)、低剂量组(n = 8)、中剂量组(n = 8)和高剂量组(n = 8)。从妊娠第7天起,每组大鼠通过灌胃给予不同剂量的维生素D,直至子代大鼠21日龄。对照组大鼠用二甲基亚砜 - 磷酸盐缓冲液喂养。子代大鼠断奶后,每组随机选取8只大鼠,雌雄数量相等。用卵清蛋白(OVA)对大鼠进行致敏,并用雾化OVA进行激发,以建立哮喘模型。对肺组织进行苏木精 - 伊红(HE)染色后检查病理变化。采用酶联免疫吸附测定(ELISA)法测定血清和支气管肺泡灌洗液(BALF)中白细胞介素 - 10(IL - 10)的浓度。采用免疫组织化学染色法检测肺组织中细胞间黏附分子 - 1(ICAM - 1)的表达。

结果

(1)肺组织病理变化:与对照组相比,光镜下可见低剂量组和中剂量组嗜酸性粒细胞浸润及气道炎症减轻,而高剂量组增加。(2)血清和BALF中IL - 浓度:血清中,与对照组[(18.7±4.7)pg/ml]相比,低剂量组[(30.2±2.8)pg/ml,P < 0.05]和中剂量组[(51.5±6.6)pg/ml,P < 0.05]中IL - 10浓度显著升高。且中剂量组IL - 10水平高于低剂量组(P < 0.05)。在BALF中,与对照组[(59.1±14.4)pg/ml]相比,中剂量组[(90.0±14.3)pg/ml,P < 0.05]中IL - 10浓度显著升高。低剂量组[(58.1±3.4)pg/ml,P > 0.05]无显著变化,而高剂量组[(45.3±6.5)pg/ml,P < 0.05]水平显著降低。(2)肺组织中ICAM - 1的表达:与对照组相比,低剂量组无显著变化(P > 0.05)。中剂量组ICAM - 1表达显著降低(P < 0.05)。高剂量组中,ICAM - 1表达显著升高(P > 0.05)。

结论

生命早期给予充足的1,25(OH)₂D₃干预可减轻大鼠哮喘模型肺组织炎症,减少嗜酸性粒细胞浸润。然而,过量可能起有害作用。其机制可能与1,25(OH)₂D₃对IL - 10分泌及ICAM - 1表达的影响有关。

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