Jiang Songling, Quan Do Van, Sung Jae Hyuck, Lee Moo-Yeol, Ha Hunjoo
Graduate School of Pharmaceutical Sciences , College of Pharmacy , Ewha Womans University , Seoul , Republic of Korea . Email:
College of Pharmacy , Dongguk University , Goyang , Republic of Korea . Email:
Toxicol Res (Camb). 2019 Oct 29;8(6):964-971. doi: 10.1039/c9tx00201d. eCollection 2019 Nov 1.
Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease. Epidemiological studies have demonstrated that cigarette smoke or nicotine is a risk factor for the progression of chronic kidney injury. The present study analyzed the kidney toxicity of cigarette smoke in experimental rats with DKD. Experimental diabetes was induced in 7-week-old Sprague-Dawley rats by a single intraperitoneal injection of streptozotocin (60 mg kg). Four weeks after the induction of diabetes, rats were exposed to cigarette smoke (200 μg L), 4 h daily, and 5 days per week for 4 weeks. Cigarette smoke did not affect the levels of plasma glucose, hemoglobin A1c, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol or non-esterified fatty acids in both control and diabetic rats under the experimental conditions. Cigarette smoke, however, significantly increased diabetes-induced glomerular hypertrophy and urinary kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) excretion, suggesting exacerbation of diabetic kidney injury. Cigarette smoke promoted macrophage infiltration and fibrosis in the diabetic kidney. As expected, cigarette smoke increased oxidative stress in both control and diabetic rats. These data demonstrated that four weeks of exposure to cigarette smoke aggravated the progression of DKD in rats.
糖尿病肾病（DKD）是终末期肾病的主要病因。流行病学研究表明，香烟烟雾或尼古丁是慢性肾损伤进展的危险因素。本研究分析了香烟烟雾对DKD实验大鼠的肾脏毒性。通过单次腹腔注射链脲佐菌素（60 mg/kg）在7周龄的斯普拉格-道利大鼠中诱导实验性糖尿病。糖尿病诱导4周后，大鼠每天暴露于香烟烟雾（200 μg/L）中4小时，每周5天，持续4周。在实验条件下，香烟烟雾对对照组和糖尿病大鼠的血糖、糖化血红蛋白、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇或非酯化脂肪酸水平均无影响。然而，香烟烟雾显著增加了糖尿病诱导的肾小球肥大以及尿肾损伤分子-1（KIM-1）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）的排泄，提示糖尿病肾损伤加重。香烟烟雾促进了糖尿病肾脏中的巨噬细胞浸润和纤维化。正如预期的那样，香烟烟雾增加了对照组和糖尿病大鼠的氧化应激。这些数据表明，暴露于香烟烟雾4周会加剧大鼠DKD的进展。
