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目的评价复方中药制剂对慢性氟中毒大鼠骨氟症的治疗效果。方法取断乳2周的纯系Wistar大鼠88只,体重为(91.1±10.0)g,按体重应用随机数字表法分为对照组16只、中氟组(染氟剂量50 mg/kg)24只、高氟组(染氟剂量100 mg/kg)24只、高氟低钙低蛋白组(染氟剂量100 mg/kg,且蛋白质与钙的含量为中氟组和高氟组的一半)24只。染氟6个月后,各组采用股动脉放血法处死8只;染氟组余下的16只大鼠再分为2个小组,一组为持续染氟阳性对照组,另一组模拟氟病区实际情况,在持续染氟的基础上应用复方制剂进行治疗;分别在治疗前、治疗后30 d和60 d时收集大鼠24 h尿样。在灌服90 d时,处死大鼠,并分离四肢骨。尿氟含量用氟离子选择电极法测定。骨氟含量采用高温灰化-氟离子选择电极法法测定。用Micro-CT(显微CT)技术检测大鼠四肢骨骨矿物质密度(BMD)、组织骨密度(TMD)、结构模型指数(SMI)、骨小梁厚度(Tb.Th)、骨小梁分离度(Tb.Sp)、各向异性(a1/a3)、骨小梁连接密度(Conn.D)、骨小梁与全部骨组织体积比(BV/TV)、骨表面积与体积比(BS/BV)、骨小梁数目(Tb.N)。结果应用复方中药治疗60 d时,中氟治疗组、高氟治疗组和高氟低钙低蛋白治疗组尿氟均低于相应的阳性对照组。用药90 d时,各治疗组骨氟亦低于相应的阳性对照组;中氟治疗组Conn.D[(1 443.81±684.09)mm~(-3)]低于中氟阳性对照组[(2 403.68±124.02)mm~(-3)];高氟治疗组TMD[(500.16±85.63)mg/cc]、Conn.D[(856.22±329.92)mm~(-3)]和BV/TV(0.44±0.04)低于相应的高氟阳性对照组[(639.96±9.51)mg/cc,(1 325.61±113.06)mm~(-3),(0.49±0.00)]。结论综合尿氟、骨氟及四肢骨BMD、BV/TV等指标改变,提示该复方中药对大鼠氟骨症具有一定的治疗效果。
Objective To evaluate the therapeutic effect of compound Chinese medicine on bone fluorosis in chronic fluorosis rats. Methods Totally 88 Wistar rats were weaned for 2 weeks. Body weight was (91.1 ± 10.0) g. According to body weight, 16 Wistar rats were randomly divided into control group (n = 24, high fluoride group (100 mg / kg), high fluoride, low calcium and low protein group (100 mg / kg dose of fluoride), and the content of protein and calcium was half 24 only. After 6 months of exposure to fluoride, 8 rats in each group were sacrificed by the femoral artery bleeding method. The remaining 16 rats in the fluoride group were further divided into two groups, one of which consisted of a continuous fluorochrome-positive control group and the other group of simulated fluorosis District, the actual situation, the continued use of fluoride compound based on the application of treatment; respectively, before treatment, 30 d and 60 d after the treatment of rats were collected 24 h urine samples. At 90 days after dosing, rats were sacrificed and the limbs were separated. Urine fluoride content was determined by fluoride ion selective electrode method. Bone fluoride content was determined by high temperature ashing - fluoride ion selective electrode method. The bone mineral density (BMD), tissue mineral density (TMD), structural model index (SMI), trabecular thickness (Tb.Th), trabecular bone (Tb.Sp), anisotropy (a1 / a3), trabecular connection density (Conn.D), trabecular bone to total bone volume ratio (BV / TV), bone surface area to volume ratio / BV), trabecular number (Tb.N). Results After 60 days of compound traditional Chinese medicine treatment, urinary fluoride in medium fluoride group, high fluoride group and high fluoride group were lower than those in corresponding positive group. At 90 days after treatment, the bone fluoridation in each treatment group was also lower than that in the corresponding positive control group. The Conn.D [(4443.81 ± 684.09) mm -3] in the fluorosis group was lower than that in the fluoride-positive control group [(2 (500.16 ± 85.63) mg / cc], Conn.D [(856.22 ± 329.92) mm ~ (-3)] and BV / TV ± 0.04) was lower than the corresponding high fluoride positive control group [(639.96 ± 9.51) mg / cc, (1325.61 ± 113.06) mm -3, (0.49 ± 0.00)]. Conclusion The changes of urinary fluoride, bone fluoride and extremities BMD, BV / TV and other indicators change, suggesting that the compound Chinese medicine on skeletal fluorosis in rats has a certain therapeutic effect.