Pan Peijiang, Wei Fumei, Jiang Junjun, Liang Bingyu, Huang Jiegang, Liao Yanyan, Su Jinming, Li Yu, Yang Xiaoyi, Chen Hui, Ye Li, Liang Hao
Bing Du Xue Bao. 2015 Mar;31(2):132-8.
The aim of this study was to investigate the influence of opiate abuse on the expression of Toll-like receptor 9 (TLR9) in the peripheral blood mononuclear cells (PBMCs) of HIV-1-infected patients and to elucidate possible mechanisms involved in the enhancement of HIV-1 replication by opiate abuse. A total of 200 participants were enrolled in the study by random selection from methadone treatment centers and voluntary HIV counseling and testing centers in the cities of Nanning, Liuzhou, and Qinzhou. These participants included 50 HIV-positive opiate abusers (Opiates HIV(+) group), 50 HIV-negative opiate abusers (Opiates HIV(-) group), 50 HIV-positive subjects who were not opiate abusers (Non-opiates HIV (+) group), and 50 HIV-negative subjects who were not opiate abusers (Control group). PBMCs were isolated from the peripheral blood samples from the subjects and the expression levels of TLR9 mRNA and protein were determined by q-PCR and western blot respectively. There was no significant difference among the four groups in age, gender, nationality, domicile, marital status, educational background or duration of drug abuse (P > 0.05). The median viral loads of the Opiates HIV(+) were significantly higher than those of the Non-Opiates HIV(+) groups (4.450 x 10(3) and 3.977 x 10(3) copies/mL respectively, P < 0.05). The relative expression levels of TLR9 mRNA in the Opiates HIV(+), Non-Opiates HIV(+), Opiates HIV(-) and Control groups were (2.13 +/- 1.59) x 10(-3), (3.66 +/- 2.22) x 10(-3), (1.96 +/- 1.42) x 10(-3) and (7.66 +/- 4.87) x 10(-3), respectively. The expression of TLR9 mRNA was significantly lower in both HIV-1-infected and -uninfected groups of opiate abusers compared with groups of non-abusers (P < 0.05). There was no significant difference in TLR9 mRNA expression levels between the Opiates HIV(+) group and the Opiates HIV(-) group (P > 0.05). However, in the non-opiate groups, the expression levels of TLR9 mRNA in the HIV(+) group were significantly lower than that of the control group (P< 0.05). Western blot results confirmed that the expression of TLR9 protein was lower in the Opiates HIV(+), Non-Opiates HIV(+), and Opiates HIV(-) groups compared to the control group. These results suggest that opiate abuse can decrease the expression of TLR9 in PBMCs, which may result in the enhancement of HIV-1 infection and replication due to a decline in immune response mediated by the TLR9 pathway.
本研究旨在探讨阿片类药物滥用对HIV-1感染患者外周血单个核细胞（PBMCs）中Toll样受体9（TLR9）表达的影响，并阐明阿片类药物滥用增强HIV-1复制的可能机制。通过从南宁市、柳州市和钦州市的美沙酮治疗中心以及自愿HIV咨询检测中心随机选取，共招募了200名参与者。这些参与者包括50名HIV阳性阿片类药物滥用者（阿片类药物HIV(+)组）、50名HIV阴性阿片类药物滥用者（阿片类药物HIV(-)组）、50名非阿片类药物滥用的HIV阳性受试者（非阿片类药物HIV(+)组）和50名非阿片类药物滥用的HIV阴性受试者（对照组）。从受试者外周血样本中分离出PBMCs，分别通过q-PCR和蛋白质印迹法测定TLR9 mRNA和蛋白质的表达水平。四组在年龄、性别、民族、户籍、婚姻状况、教育背景或药物滥用持续时间方面无显著差异（P>0.05）。阿片类药物HIV(+)组的病毒载量中位数显著高于非阿片类药物HIV(+)组（分别为4.450×10(3)和3.977×10(3)拷贝/mL，P<0.05）。阿片类药物HIV(+)组、非阿片类药物HIV(+)组、阿片类药物HIV(-)组和对照组中TLR9 mRNA的相对表达水平分别为(2.13±1.59)×10(-3)、(3.66±2.22)×10(-3)、(1.96±1.42)×10(-3)和(7.66±4.87)×10(-3)。与非滥用组相比，阿片类药物滥用的HIV-1感染组和未感染组中TLR9 mRNA的表达均显著降低（P<0.05）。阿片类药物HIV(+)组和阿片类药物HIV(-)组之间TLR9 mRNA表达水平无显著差异（P>0.05）。然而，在非阿片类药物组中，HIV(+)组TLR9 mRNA的表达水平显著低于对照组（P<0.05）。蛋白质印迹结果证实，与对照组相比，阿片类药物HIV(+)组、非阿片类药物HIV(+)组和阿片类药物HIV(-)组中TLR9蛋白的表达较低。这些结果表明，阿片类药物滥用可降低PBMCs中TLR9的表达，这可能由于TLR9途径介导的免疫反应下降导致HIV-1感染和复制增强。
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