海洛因成瘾者不同戒断时间肠道屏障损伤血清标志物的研究

Study on Serum Markers of Intestinal Barrier Damage in Heroin Addicts at Different Withdrawal Times

目的分析不同戒断时间内肠道屏障损伤标志物的变化,研究海洛因戒断后肠屏障损伤的机制,为海洛因戒断后精神症状改变和肠屏障之间的关系提供新的方向。方法招募14名海洛因戒断1周(HWS1W),24名海洛因戒断3月(HWS3M)的人群和26名健康者为对照组(HCs),用ELISA法测定血清iFABP、D-LDH、DAO、LBP、Zonulin和BDNF。结果HWS1W组的血清D-LDH、DAO、LBP、Zonulin和BDNF水平均明显高于HCs组(P<0.001)。HWS3M组的血清iFABP、D-LDH、DAO和BDNF明显高于HCs组(P<0.001)。DAO在海洛因戒断1周时明显升高,3个月时明显降低,但仍高于健康对照组(P<0.001)。iFABP在急性戒断期(1周)没有变化,但在戒断的3个月左右增加。LBP和Zonulin在海洛因戒断组约1周内明显增加,但在HWS3M组和HCs组之间差异无统计学意义(P>0.05)。HWS1W组和HWS3M组的D-LDH和BDNF的水平明显增加(P<0.001)。结论海洛因戒断1周和3个月均发生肠屏障功能损伤。戒断1周后,肠屏障损伤可能与肠道菌群紊乱、紧密连接蛋白变化、肠道炎症和肠上皮完整性损伤有关。戒断3个月后,肠屏障损伤更可能是肠屏障上皮持续损伤造成的。

Objective To investigate the mechanisms of intestinal barrier damage after heroin withdrawal by analyzing changes in markers of intestinal barrier damage at different withdrawal times,providing a new direction for the relationship between altered psychiatric symptoms and the intestinal barrier after heroin withdrawal.Methods 141-week heroin withdrawal subjects(HWS1W),243-months heroin withdrawal subjects(HWS3M)and 26 healthy controls(HCs)were recruited,and serum iFABP,D-LDH,iFABP,DAO,LBP,Zonulin,BDNF and D-LDH were determined by ELISA.Results Serum D-LDH,DAO,LBP,Zonulin and BDNF levels in HWS1W group were significantly higher than those in HCs(P<0.001).Serum iFABP,D-LDH,DAO,and BDNF in HWS3M group were significantly higher than those in HCs group(P<0.001).DAO increased significantly at 1 week of heroin withdrawal and decreased significantly at 3 months,but was still higher than the healthy control group(P<0.001).iFABP showed no change in the acute withdrawal period(1 week),but increased at about 3 months of withdrawal.LBP and Zonulin increased significantly in the heroin abstention group for about one week,but there was no significant difference between the HWS3M group and the HCs group(P>0.05).The levels of DLDH and BDNF were significantly increased in HWS1W and HWS3M groups(P<0.001).Conclusions The present study showed that intestinal barrier dysfunction occurred both 1 week and 3 months after heroin withdrawal.After 1 week of abstinence,intestinal barrier damage may be associated with intestinal flora disorder,changes in tight junction proteins,intestinal inflammation and intestinal epithelial integrity damage.After 3 months of abstinence,intestinal barrier damage is more likely to result from persistent damage to the intestinal barrier epithelium.