Hajiasgharzadeh Khalil, Shahabi Parviz, Karimi-Sales Elham, Alipour Mohammad Reza
Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Clin Exp Hepatol. 2024 Mar;10(1):62-71. doi: 10.5114/ceh.2024.136227. Epub 2024 Mar 15.
Liver fibrosis and cigarette smoking seem to be directly linked. Nicotine, as an agonist of nicotinic acetylcholine receptors (nAChRs), induces many downstream signaling pathways. The pathways through which nicotine affects the process of liver fibrosis have not been clarified. The present study aimed to investigate the nicotine-induced effects on fibrosis progression in cholestatic rats.
First, the Wistar rats were subjected to sham or bile duct ligation (BDL) surgery. The rats were treated with low and high doses of nicotine (1 or 10 mg/kg) for three weeks. They were monitored for their body weights before and 21 days after BDL. Also, spleens were weighed to calculate the spleen/body weight ratio. Ductular proliferation and fibrosis were evaluated using hematoxylin and eosin (H&E) as well as Masson's trichrome staining. The mRNA expression of α4nAChR, α7nAChR, and fibrosis gene α-smooth muscle actin (α-SMA) was measured by real-time PCR.
The findings showed that nicotine promotes the development of BDL-induced liver fibrosis. The ratio of spleen/body weight was significantly affected by nicotine exposure. H&E and Masson's trichrome staining showed that the level of liver fibrosis was higher in the cholestatic BDL groups, and this effect was significantly augmented in the nicotine-treated rats. Also, α4nAChR, α7nAChR, and α-SMA expression was observed in the BDL rats and increased following nicotine treatment.
The activation of nAChR triggers biliary proliferation and liver fibrosis. Studying the intracellular mechanism of nicotine and alteration in the expression of nicotinic receptors following nicotine exposure can be useful both in diagnosing nicotine-related diseases and finding new treatment strategies.
肝纤维化与吸烟似乎直接相关。尼古丁作为烟碱型乙酰胆碱受体（nAChRs）的激动剂，可诱导许多下游信号通路。尼古丁影响肝纤维化进程的具体途径尚未明确。本研究旨在探讨尼古丁对胆汁淤积性大鼠纤维化进展的影响。
首先，对Wistar大鼠进行假手术或胆管结扎（BDL）手术。大鼠分别接受低剂量和高剂量尼古丁（1或10mg/kg）治疗三周。在BDL手术前及术后21天监测大鼠体重。同时，称量脾脏重量以计算脾/体重比。采用苏木精-伊红（H&E）染色及Masson三色染色评估胆管增生和纤维化情况。通过实时PCR检测α4nAChR、α7nAChR及纤维化基因α-平滑肌肌动蛋白（α-SMA）的mRNA表达。
研究结果表明，尼古丁促进BDL诱导的肝纤维化发展。尼古丁暴露显著影响脾/体重比。H&E染色及Masson三色染色显示，胆汁淤积性BDL组的肝纤维化程度更高，且在尼古丁处理的大鼠中这种作用显著增强。此外，在BDL大鼠中观察到α4nAChR、α7nAChR及α-SMA表达，且尼古丁处理后表达增加。
nAChR的激活引发胆管增生和肝纤维化。研究尼古丁的细胞内机制以及尼古丁暴露后烟碱型受体表达的变化，对于诊断尼古丁相关疾病和寻找新的治疗策略均具有重要意义。
