阿苯达唑对肝泡型包虫病患者外周血单个核细胞T-bet及GATA3 mRNA表达的影响及意义

Influence of oral administration of Albendazole on the expression of T-bet and GATA3 mRNA of peripheral blood mononuclear cells in patients with hepatic alveolar echinococcosis and its significance

目的 探讨阿苯达唑对肝泡型包虫病患者外周血单个核细胞中转录因子T-bet和GATA3mRNA表达的影响及意义.方法 回顾性分析2013年4月至11月新疆医科大学第一附属医院收治的55例受试者的临床资料.其中肝泡型包虫病患者服用阿苯达唑15例,纳入药物组;肝泡型包虫病首治患者14例,纳入肝泡型包虫病组;健康志愿者26例,纳入健康志愿者组.药物组患者口服片剂阿苯达唑10 mg/（kg ·d）,用药时间为（2.5±2.3）年.所有受试者在入组后第2天清晨空腹抽取外周血.采用实时荧光定量PCR法检测各组受试者外周血单个核细胞T-bet和GATA3 mRNA的表达,同时运用ELISA法检测受试者血浆IFN-γ、IL-5的表达.正态分布数据以（x）±s表示,偏态分布数据以M表示,组间比较用单因素方差分析,两两比较采用LSD-t法,用直线相关分析探讨两因素之间相关关系.结果 药物组、肝泡型包虫病组和健康志愿者组受试者外周血单个核细胞T-bet mRNA中位值分别为0.117、0.114、0.094,3组比较,差异无统计学意义（F =0.34,P＞0.05）;药物组、肝泡型包虫病组和健康志愿者组受试者外周血单个核细胞GATA3mRNA表达水平中位值分别为0.006、0.007、0.021,3组比较,差异有统计学意义（F =4.96,P＜0.05）;药物组、健康志愿者组和肝泡型包虫病组受试者T-bet与GATA3的比值（T-bet/GATA3）中位值分别为25.618、8.235、4.350,3组比较,差异有统计学意义（F=9.12,P＜0.05）.药物组、肝泡型包虫病组和健康志愿者组受试者血浆IFN-γ表达水平分别为（367±252） μg/L、（305±52） μg/L、（326±122） μg/L,3组比较,差异无统计学意义（F=0.52,P＞0.05）;药物组、肝泡型包虫病组和健康志愿者组受试者血浆IL-5表达水平分别为（40±8）μg/L、（52±39） μg/L、（41±6）μg/L,3组比较,差异无统计学意义（F=1.85,P＞0.05）;药物组、健康志愿者组和肝泡型包虫病组受试者IFN-γ与IL-5的比值分别为9.5±9.2、6.8±2.1、8.0±2.8,3组比较,差异无统计学意义（F=1.18,P＞0.05）.药物组患者阿苯达唑用药时间和T-bet/GATA3之间无相关性（r=0.076,P＞0.05）.结论 肝泡型包虫病患者口服阿苯达唑后明显上调T-bet/GATA3,逆转Th1/Th2细胞失衡,Th1细胞杀伤多房棘球蚴的能力明显增强,而Th2细胞保护多房棘球蚴的能力有所减弱.机体的保护性免疫应答有所恢复.外周血T-bet/GATA3可作为阿苯达唑治疗肝泡型包虫病疗效评价的随访指标.

Objective To investigate the influence of Albendazole (ABZ) on the expression of T-bet and GATA3 mRNA of peripheral blood mononuclear cells in patients with hepatic alveolar echinococcosis (HAE) and its significance.Methods The clinical data of 55 individuals in the First Affiliated Hospital of Xinjiang Medical University from April to November 2013 were retrospectively analyzed.Fifteen patients with HAE who received ABZ orally were in the HAE + ABZ group,15 patients with HAE were in the HAE group,and 26 healthy individuals were in the healthy donor group.ABZ was administered with dosage of 10 mg/(kg · d) for (2.5 ± 2.3)years.The peripheral blood was drawn at the second day.The mRNA expressions of T-bet and GATA3 in the peripheral mononuclear cells were detected by real-time PCR.The plasma levels of interferon-γ (IFN-γ) and interleukin-5 (IL-5) were detected by enzyme linked immunosorbent assay (ELISA).Normal distribution data were presented by (x) ± s and skewed distribution data were presonted by M.Data were analyzed using the analysis of variance or LSD-t test,and the correlation of 2 factors was analyzed using the linear correlation analysis.Results The median value of the expression of T-bet in the HAE + ABZ group,the HAE group and the healthy donor group were 0.117,0.114,0.094,with no significant difference between the 3 groups (F =0.34,P > 0.05).The median value of the expressions of the GATA3 in the HAE + ABZ group,the HAE group and the healthy donor group were 0.006,0.007,0.021,with significant difference between the 3 groups (F =4.96,P ＜ 0.05).The median value of the ratios of T-bet to GATA3 in the HAE + ABZ group,the HAE group and the healthy donor group were 25.618,8.235,4.350,with significant difference between the 3 groups (F =9.12,P ＜0.05).The expressions of IFN-γ in the HAE + ABZ group,the HAE group and the healthy donor group were (367 ± 252) μg/L,(305 ± 52)μg/L and (326 ± 122) μg/L,with no significant difference between the 3 groups (F =0.52,P ＞ 0.05).The expressions of IL-5 in the HAE + ABZ group,the HAE group and the healthy donor group were (40 ± 8)μg/L,(52 ±39)μg/L and (41 ±6)μg/L,with no significant difference between the 3 groups (F =1.85,P ＞0.05).The ratios of IFN-γto IL-5 in the HAE + ABZ group,the HAE group and the healthy donor group were 9.5 ± 9.2,6.8 ±2.1 and 8.0 ± 2.8,with no significantly difference between the 3 groups (F =1.18,P ＞ 0.05).There was no correlation between the administration time of ABZ and the ratio of T-bet to GATA3 in the HAE + ABZ group (r =0.076,P ＞ 0.05).Conclusions The ratio of T-bet to GATA3 is significantly increased after administration of ABZ,and the Th1/Th2 immune response is skewed towards Th1 cells to enhance the parasite elimination,and thus the Th2 cells response is weakened.The ratio of T-bet to GATA3 may be the indicator for evaluating the efficacy of ABZ in the treatment of HAZ.