丹蓝仙硼疗氟胶囊对氟中毒大鼠骨保护素/核因子κβ受体活化因子配体/核因子κβ受体活化因子系统表达水平的影响

Effect of fluoride on the expression of osteoprotegerin/receptor activator of nuclear factor κβ ligand/receptor activator of nuclear factor κβ system proteins of rats with fluorosis and the antagonism of Danlan Xianpeng capsule

目的 观察慢性氟中毒大鼠骨组织中骨保护素（OPG）、核因子κβ受体活化因子配体（RANKL）、核因子κβ受体活化因子（RANK）蛋白表达水平,探讨OPG/RAN KL/RANK系统与慢性氟中毒大鼠骨骼损伤的关系及丹蓝仙硼疗氟胶囊的拮抗作用.方法 将SD大鼠按体质量随机分为6组（组内雌雄各半）：氟中毒组、高剂量药物组、中剂量药物组、低剂量药物组、对照组、硼砂（阳性药物对照）组,每组12只.对照组饮用自来水,其余5个实验组饮用含氟水（50 mg/L）,而高、中、低剂量药物组另摄入丹蓝仙硼疗氟胶囊,剂量分别为0.8、O.4、O.2 g/kg,硼砂组另摄入硼砂,剂量为0.8 g/kg.6个月时用免疫组织化学方法检测OPG、RANKL、RANK蛋白在大鼠股骨干骺端的表达.结果 与对照组（173.79±5.23、174.17±5.O1、155.63±7.11）比较,氟中毒组大鼠股骨干骺端OPG、RANKL（156.83±5.80、157.74±6.70）表达增高,RANK（173.92±4.37）表达降低,差异有统计学意义（P均＜0.05）.与氟中毒组比较,高、中剂量药物组OPG、RANKL（169.67±5.07、168.08±5.05,170.78±5.01、168.41±7.19）表达降低,RANK（162.12±4.24、166.69±5.78）表达增高,差异有统计学意义（P均＜O.05）.与硼砂组（167.27±4.08、167.85±5.O1、166.14±3.95）比较,低剂量药物组OPG、RANKL（163.40±4.11、159.49±5.78）表达增高,RANK（171.54±8.06）表达降低,而高剂量药物组RANK（162.12±4.24）表达增高,差异有统计学意义（P均＜0.05）.结论 慢性氟中毒可引起成骨与破骨活动均增强的骨转换增高状态,并可通过改变OPG/RANKL/RANK系统表达影响骨吸收的程度.丹蓝仙硼疗氟胶囊能通过OPG/RANKL/RANK系统影响骨重建,对氟致骨损伤有拮抗作用.

Objective To observe the expression of osteoprotegerin （OPG）, receptor activator of nuclear factor κβ ligand（RANKL） and receptor activator of nuclear factor κβ （RANK） in bone tissue of rats with chronic fluorosis and to explore the relation between OPG/RANKL/RANK system and bone damage in chronic fluoride poisoning rat and the antagonism effects of Danlan Xianpeng capsule. Methods SD rats were randomly divided into six groups according to body weight （equal male and female in each group）： fluorosis group, high dose drug group, medium dose drug group, low dose drug group, control group, borax group（positive control）, 12 rats in each group. The control group drank tap water and the remaining 5 experimental groups consumed 50 mg/L fluoride water, and high, medium and low doses drug group took Danlan Xianpeng capsule at doses of 0.8,0.4,0.2 g/kg,borax group took borax at dose of 0.8 g/kg. OPG, RANKL, RANK protein in rat tibial metaphysis was detected by immunohistochemistry at the 6 month. Results Compared with the control group（173.79 ± 5.23, 174.17 ± 5.01,155.63 ± 7.11）, the expressions of OPG, RANKL were increased and the expression of RANK was decreased in fluorosis group（156.83 ± 5.80, 157.74 ± 6.70, 173.92 ± 4.37）, the difference was statistically significant （all P 〈 0.05）. Compared with the fluorosis group, the expression of OPG and RANKL were decreased and the expression of RANK was increased in high-dose drug group, middle-dose drug group（169.67±5.07, 168.08 ± 5.05,162.12 ± 4.24, 170.78 ± 5.01, 168.41 ± 7.19, 166.69 ± 5.78, all P 〈 0.05）. Compared with the borax group （167.27 ± 4.08, 167.85 ± 5.01, 166.14 ± 3.95）, the expression of OPG and RANKL was increased in the low-dose drug group （163.40 ± 4.11, 159.49 ± 5.78）, the expression of RANK was increased in the high-dose drug group （162.12 ± 4.24） and decreased in the low-dose drug group（171.54 ± 8.06）, the difference was statistically significant （all P 〈 0.05）. Conclusions Chronic fluoride poisoning can cause increased bone turnover and enhance the activity of osteoelastic absorption by increasing RANKL. Danlan Xianpeng capsule can affect bone remodeling through the OPG/RANKL/RANK system, and antagonises bone damage caused by fluoride.