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目的探讨铅中毒对大鼠机体骨代谢影响及机制。方法选取21日龄SPF级雄性SD大鼠40只,适应性喂养7 d后,随机分为4组:对照组(去离子水)、低、中、高剂量铅组(0.1%、0.2%、0.3%醋酸铅水);饲养60 d后,称重;取大鼠后肢股骨,ICP法测定股骨中Pb、Ca含量;采用常规苏木素-伊红染色法(HE)对大鼠骨组织形态进行观察;应用荧光定量RT-PCR法测定大鼠骨骼中过氧化物酶体增长因子活化受体γ(PPAR-γ)、Wnt2、转录因子1(Tcf-1)、和β-catenin基因表达量。结果与对照组比较,随着染铅剂量增加,低、中、高剂量铅组大鼠骨骼铅含量[分别为(0.221 5±0.033 0)、(0.335 3±0.040 7)、(0.399 2±0.030 9)mg/g]均升高,而骨钙含量[分别为(21.7194±1.120 8)、(21.559 5±1.094 0)、(21.421 7±0.700 2)mg/g]均下降,差异均有统计学意义(P<0.05);与对照组比较,低、中剂量铅组大鼠骨小梁相对变薄、变细,高剂量铅组大鼠股骨骨小梁稀疏、变细、变薄或断裂,骨髓腔相对扩大;与对照组比较,高剂量铅组大鼠骨骼中PPAR-γ、Wnt2、Tcf-1及β-catenin m RNA表达量[分别为(0.821 3±0.0202)、(0.852 6±0.030 8)、(0.874 3±0.077 2)、(0.874 5±0.055 3)]均下降,差异均有统计学意义(P<0.05)。结论铅对大鼠骨组织中钙的吸收具有抑制作用,对骨组织结构具有损伤作用,其机制可能与下调骨骼中PPAR-γ、Wnt2、Tcf-1及β-catenin基因表达有关。
Objective To investigate the effect of lead poisoning on bone metabolism in rats and its mechanism. Methods Forty SPF male Sprague-Dawley (SD) rats of 21 days old were randomly divided into 4 groups: control group (deionized water), low, medium and high dose lead group (0.1%, 0.2% 0.3% lead acetate in water). After feeding for 60 days, the rats were weighed. The hindlimb femur was collected and the contents of Pb and Ca in the femur were measured by ICP. The morphology of the rat bone was observed by conventional hematoxylin-eosin staining (HE) The expression of peroxisome proliferator activated receptor γ (PPAR-γ), Wnt2, Tcf-1 and β-catenin in rat bone were measured by real-time fluorescence quantitative RT-PCR. Results Compared with the control group, the lead levels in the low, middle and high dose lead groups [(0.221 5 ± 0.033 0), (0.335 3 ± 0.040 7) and (0.399 2 ± 0.030 9) mg / g], while the content of bone calcium [(21.7194 ± 1.120 8), (21.559 5 ± 1.094 0), (21.421 7 ± 0.700 2) mg / g] (P <0.05). Compared with the control group, the trabecular bone became thinner in the low and medium dose lead groups, and the trabeculae became thinner, thinner, thinner or thinner in the thin and high dose lead groups , Compared with the control group, the expression of PPAR-γ, Wnt2, Tcf-1 and β-catenin m RNA in the bones of high dose lead group were (0.821 3 ± 0.0202) and (0.852 6 ± 0.030 8), (0.874 3 ± 0.077 2), (0.874 5 ± 0.055 3)], all of which were significantly different (P <0.05). Conclusion Lead has an inhibitory effect on the absorption of calcium in rat bone tissue, which may impair the structure of bone. The mechanism may be related to down-regulating the expression of PPAR-γ, Wnt2, Tcf-1 and β-catenin in bone.