Hapidin Hermizi, Othman Faizah, Soelaiman Ima-Nirwana, Shuid Ahmad N, Luke Douglas A, Mohamed Norazlina
Department of Anatomy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
J Bone Miner Metab. 2007;25(2):93-8. doi: 10.1007/s00774-006-0733-9. Epub 2007 Feb 26.
The effects of nicotine administration on bone-resorbing cytokines, cotinine, and bone histomorphometric parameters were studied in 21 Sprague-Dawley male rats. Rats aged 3 months and weighing 250-300 g were divided into three groups. Group 1 was the baseline control (BC), which was killed without treatment. The other two groups were the control group (C) and the nicotine-treated group (N). The N group was treated with nicotine 7 mg/kg body weight and the C group was treated with normal saline only. Treatment was given by intraperitoneal injection for 6 days/week for 4 months. The rats were injected intraperitoneally with calcein 20 mg/kg body weight at day 9 and day 2 before they were killed. ELISA test kits were used to measure the serum interleukin-1 (IL-1), interleukin-6 (IL-6), and cotinine (a metabolite of nicotine) levels at the beginning of the study and upon completion of the study. Histomorphometric analysis was done on the metaphyseal region of the trabecular bone of the left femur by using an image analyzer. Biochemical analysis revealed that nicotine treatment for 4 months significantly increased the serum IL-1, IL-6, and cotinine levels as compared to pretreatment levels. In addition, the serum cotinine level was significantly higher in the N group than in the C group after 4 months treatment. Histomorphometric analysis showed that nicotine significantly decreased the trabecular bone volume (BV/TV), trabecular thickness (Tb.Th), double-labeled surface (dLS/BS), mineralizing surface (MS/BS), mineral appositional rate (MAR), and bone formation rate (BFR/BS), while causing an increase in the single-labeled surface (sLS/BS), osteoclast surface (Oc.S/BS), and eroded surface (ES/BS) as compared to the BC and C groups. In conclusion, treatment with nicotine 7 mg/kg for 4 months was detrimental to bone by causing an increase in the bone resorbing cytokines and cotinine levels. Nicotine also exerted negative effects on the dynamic trabecular histomorphometric parameters.
在21只雄性Sprague-Dawley大鼠中研究了尼古丁给药对骨吸收细胞因子、可替宁及骨组织形态计量学参数的影响。3月龄、体重250 - 300 g的大鼠被分为三组。第1组为基线对照组（BC），未经处理即处死。另外两组为对照组（C）和尼古丁处理组（N）。N组用7 mg/kg体重的尼古丁处理，C组仅用生理盐水处理。每周6天经腹腔注射给药，持续4个月。在处死前第9天和第2天，给大鼠腹腔注射20 mg/kg体重的钙黄绿素。在研究开始时和研究结束时，使用ELISA检测试剂盒测量血清白细胞介素-1（IL-1）、白细胞介素-6（IL-6）和可替宁（尼古丁的一种代谢产物）水平。使用图像分析仪对左股骨小梁骨的干骺端区域进行组织形态计量学分析。生化分析显示，与预处理水平相比，尼古丁处理4个月显著提高了血清IL-1、IL-6和可替宁水平。此外，处理4个月后，N组血清可替宁水平显著高于C组。组织形态计量学分析表明，与BC组和C组相比，尼古丁显著降低了小梁骨体积（BV/TV）、小梁厚度（Tb.Th）、双标记表面（dLS/BS）、矿化表面（MS/BS）、矿物质沉积率（MAR）和骨形成率（BFR/BS），同时导致单标记表面（sLS/BS）、破骨细胞表面（Oc.S/BS）和侵蚀表面（ES/BS）增加。总之，7 mg/kg尼古丁处理4个月通过增加骨吸收细胞因子和可替宁水平对骨骼有害。尼古丁对动态小梁组织形态计量学参数也有负面影响。
