Department of Medicine, University of Szeged, Szeged, Hungary.
MTA-SZTE Momentum Epithelial Cell Signaling and Secretion Research Group, University of Szeged, Szeged, Hungary.
Clin Transl Med. 2024 Jun;14(6):e1733. doi: 10.1002/ctm2.1733.
Smoking is recognised as an independent risk factor in the development of chronic pancreatitis (CP). Cystic fibrosis transmembrane conductance regulator (CFTR) function and ductal fluid and bicarbonate secretion are also known to be impaired in CP, so it is crucial to understand the relationships between smoking, pancreatic ductal function and the development of CP.
We measured sweat chloride (Cl) concentrations in patients with and without CP, both smokers and non-smokers, to assess CFTR activity. Serum heavy metal levels and tissue cadmium concentrations were determined by mass spectrometry in smoking and non-smoking patients. Guinea pigs were exposed to cigarette smoke, and cigarette smoke extract (CSE) was prepared to characterise its effects on pancreatic HCO and fluid secretion and CFTR function. We administered cerulein to both the smoking and non-smoking groups of mice to induce pancreatitis.
Sweat samples from smokers, both with and without CP, exhibited elevated Cl concentrations compared to those from non-smokers, indicating a decrease in CFTR activity due to smoking. Pancreatic tissues from smokers, regardless of CP status, displayed lower CFTR expression than those from non-smokers. Serum levels of cadmium and mercury, as well as pancreatic tissue cadmium, were increased in smokers. Smoking, CSE, cadmium, mercury and nicotine all hindered fluid and HCO secretion and CFTR activity in pancreatic ductal cells. These effects were mediated by sustained increases in intracellular calcium ([Ca]), depletion of intracellular ATP (ATP) and mitochondrial membrane depolarisation.
Smoking impairs pancreatic ductal function and contributes to the development of CP. Heavy metals, notably cadmium, play a significant role in the harmful effects of smoking.
Smoking and cigarette smoke extract diminish pancreatic ductal fluid and HCO secretion as well as the expression and function of CFTR Cd and Hg concentrations are significantly higher in the serum samples of smokers Cd accumulates in the pancreatic tissue of smokers.
吸烟被认为是慢性胰腺炎（CP）发展的独立危险因素。囊性纤维化跨膜电导调节因子（CFTR）的功能以及胰管液体和碳酸氢盐的分泌也已知在 CP 中受损，因此了解吸烟、胰管功能与 CP 发展之间的关系至关重要。
我们测量了有和没有 CP 的吸烟者和非吸烟者的汗液氯化物（Cl）浓度，以评估 CFTR 活性。通过质谱法测定了吸烟和非吸烟患者的血清重金属水平和组织镉浓度。用香烟烟雾暴露豚鼠，并制备香烟烟雾提取物（CSE）以表征其对胰腺 HCO 3 和液体分泌和 CFTR 功能的影响。我们给吸烟和非吸烟组的小鼠注射 Cerulein 以诱导胰腺炎。
与非吸烟者相比，吸烟者（无论是否患有 CP）的汗液样本中 Cl 浓度升高，表明 CFTR 活性因吸烟而降低。与非吸烟者相比，无论 CP 状态如何，吸烟者的胰腺组织中 CFTR 表达水平均较低。吸烟者的血清镉和汞水平以及胰腺组织镉水平升高。吸烟、CSE、镉、汞和尼古丁均抑制胰腺导管细胞的液体和 HCO 3 分泌以及 CFTR 活性。这些作用是通过细胞内钙（[Ca]）持续增加、细胞内 ATP（ATP）耗竭和线粒体膜去极化介导的。
吸烟会损害胰腺导管功能并导致 CP 的发生。重金属，特别是镉，在吸烟的有害影响中起重要作用。
吸烟和香烟烟雾提取物会减少胰腺导管的液体和 HCO 3 分泌，以及 CFTR 的表达和功能。吸烟者的血清样本中 Cd 和 Hg 浓度显著升高。吸烟者的胰腺组织中 Cd 蓄积。
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