普萘洛尔对去卵巢大鼠胫骨骨形态的影响

背景普萘洛尔是非选择性竞争抑制肾上腺β受体阻滞剂,具有拮抗交感神经兴奋作用,而绝经后骨质疏松的发生与交感神经活性的改变可能存在联系.目的观察普萘洛尔对去卵巢大鼠骨形态的影响,并与雌激素治疗结果进行比较.设计完全随机设计,对照实验.单位解放军北京军区总医院内分泌科.材料实验于2002-03/2003-04在中国中医研究基础理论研究所动物室完成.选用6月龄雌性未交配SD大鼠40只.将40只大鼠随机分为4组,每组10只假手术组,雌激素治疗组,普萘洛尔治疗组,安慰剂组.方法①雌激素治疗组和普萘洛尔治疗组及安慰剂组大鼠麻醉后,开腹,结扎切除双侧卵巢后.假手术组打开腹腔后切除卵巢周围一小块脂肪组织后关腹.②雌激素治疗组采用17?-雌二醇谷物油溶解后皮下注射20 μg/(kg·d);普萘洛尔治疗组采用普萘洛尔8 mg/(kg·d)胃内灌注.安慰剂组及假手术组给予与治疗组等量的谷物油皮下注射和/或蒸馏水灌胃.2个治疗组在治疗措施的同时,给予与安慰剂组及假手术组相同的干预措施.各组均在术后1周给药,共干预12周.③采用LeicaQwin图像分析系统进行骨组织形态计量,观察骨小梁体积百分比、活性生成表面百分比、骨小梁矿化率、骨小梁骨生成率指标的变化.④显著性差异性比较采用t检验.主要观察指标各组大鼠胫骨骨形态计量结果比较.结果大鼠40只,每组10只均进入结果分析.①大鼠左侧胫骨活性生成表面百分比和骨小梁矿化率假手术组和雌激素治疗组明显低于安慰剂组(P＜0.01),普萘洛尔治疗组明显高于安慰剂组(P＜0.05).②大鼠左侧胫骨骨小梁骨生成率普萘洛尔治疗组明显高于安慰剂组(P＜0.05).③大鼠左侧胫骨骨小梁体积百分比假手术组和普萘洛尔治疗组明显高于安慰剂组(P＜0.01),普萘洛尔治疗组明显低于假手术组和雌激素治疗组(P＜0.01).结论普萘洛尔能使卵巢切除术后骨质疏松大鼠的骨量增加,抑制骨丢失,促进骨形成,对大鼠质疏松有明显的防治作用.

Changes of tibial morphology due to propranolol medication in ovariectomized rats

BACKGROUND: Propranolol is a nonselective competitive adrenergic β-receptor blocker capable of suppressing sympathetic nerve excitation. Postmenstrual osteoporosis may be associated with the changes of sympathetic nerve activity.OBJECTIVE: To observe the effect of propranolol on tibial morphology in ovariectomized rats, and compare it with that of estrogen medication.DESIGN: Completely randomized design and controlled experiment.SETTING: End ocrinology Department, General Hospital of Beijing Military Area Command of Chinese PLA.MATERIALS: This experiment was conducted at the animal laboratory of the Institute of Basic Theory Research of Traditional Chinese Medicine between March 2002 and April 2003. Forty female unmated SD rats aged 6 months were included and randomized into 4 groups with 10 rats in each group: sham-operation group, estrogen medication group, propranolol treatment group, and placebo group.METHODS: ① Rats in estrogen group, propranolol treatment group and placebo group were anesthetized before the abdomen was opened and bilateral ovaries were excised. Rats in sham-operation group had their abdominal cavity opened and a piece of ovary surrounding fattytissue excised before closing the abdomen. ② Estrogen medication group: Rats were given hypodermic injection of grain oil dissolved 17 β-estradiol at a dose of 20 μg/(kg·d). Propranolol treatment group: Propranolol was used for gastric infusion at a dose of 18 mg/(kg·d). Placebo group and sham-op-eration group: The same volume of grain oil and/or distilled water was used instead of hypodermic injection or gastric infusion. Two treatment groups were given the same intervention as placebo group and sham-operation group during treatment; medication was carried out from postoperative week 1 for altogether 12 weeks. ③ Leica Qwin imaging analysis system was used for morphological measurement of bone tissues so as to calculate the volume percentage, active-surface formation percentage, mineralization rate, and formation rate of bone trabecula. ④ t-test was used for comparing the differences.MAIN OUTCOME MEASURES: Comparison of rat tibial morphological parameters between groups.RESULTS: Forty rats were divided into four groups with 10 rats in each and all entered the result analysis. ① Left tibial active-surface formation percentage and mineralization rate of bone trabecula: They were obviously lower in sham-operation group and estrogen group than in placebo group (P ＜ 0.01), but obviously higher in propranolol treatment group than placebo group (P ＜ 0.05). ② Formation rate of left tibial trabecula: It was obviously higher in propranolol treatment group than in placebo group (P ＜ 0.05). ③ The volume percentage of left tibial bone trabecula: It was obviously higher in sham-operation group and propranolol treat ment group than in placebo group (P ＜ 0.01), but obviously lower in pro pranolol treatment group than in sham-operation group and estrogen group (P ＜ 0.01). CONCLUSION: Propranolol can increase bone mass, reduce bone loss, and promote bone formation in osteoporotic rats following ovariectomy, thus displaying obvious preventive and therapeutic effects on osteoperesis in rats.