An investigation on the best time period for observation of disuse osteoporosis in rats

目的 建立废用性骨质疏松动物模型,探讨发生废用性骨质疏松的最佳时间段.方法 选取3个月龄SD大鼠78只,其中的72只大鼠随机均分为假手术组(S组)和模型组(M组),每组根据术后检测时间(1、2、4、6、8、12周)的时间段分为6个亚组,每组6只.另6只为空白对照组(BC组).检测血清骨钙蛋白(BGP)、碱性磷酸酶(ALP)、抗酒石酸酸性磷酸酶(Strap)及尿羟脯氨酸与尿肌酐比值(HOP/Cr)；进行左胫骨近侧干骺段HE染色和Masson染色,观察骨组织形态学.结果 随着去神经时间的延长,M组BGP和尿HOP/Cr逐渐降低,而ALP和Strap逐渐升高,4、6、8、12周的水平与1、2周差异明显(P＜0.05),而术后4、6、8、12周之间的差异无统计学意义(P＞0.05).M组骨皮质变薄、孔隙增多、骨小梁稀疏、纤细并有多处断裂,小梁间吻合减少,骺板下区空旷,髓腔扩大,破骨细胞数增多.Masson染色见随着废用时间的延长,新生胶原的量也在减少.结论 坐骨神经切断术是建立废用性骨质疏松动物模型的有效方法.在废用性骨质疏松形成过程中,骨形成显著持续降低,但速度趋缓,观察的最佳时间为造模后4-6周.     

强骨胶囊联合骨瓜提取物注射液治疗骨质疏松性股骨骨折的临床研究

目的探讨强骨胶囊联合骨瓜提取物注射液治疗骨质疏松性股骨骨折的临床效果。方法选取2015年6月—2017年6月上海市浦东新区光明中医院收治的98例骨质疏松性股骨骨折患者,随机分为对照组和治疗组,每组各49例。对照组静脉滴注骨瓜提取物注射液,100 mg加入250 m L生理盐水均匀混合,1次/d,连续治疗20 d为1个疗程,停药10 d;再按以上方案连用3个疗程。治疗组在对照组治疗基础上口服强骨胶囊,1粒/次,3次/d。两组均连续治疗3个月。观察两组的临床疗效,比较两组治疗1、3个月时骨痂骨密度(BMD)水平和骨愈合时间。比较两组治疗前后VAS评分、股骨颈BMD、HHS评分、钙(Ca)、磷(P)、碱性磷酸酶(ALP)、骨钙素(BGP)、24 h尿标本中羟脯氨酸(HOP)水平的变化情况。结果治疗后,对照组和治疗组的总有效率分别为79.59%、93.88%,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组治疗1、3个月时骨痂BMD值显著高于对照组治疗同期,治疗组骨折愈合时间显著短于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组VAS评分、Ca、ALP水平和24 h尿HOP显著降低,股骨颈BMD、HHS评分、P、BGP显著升高,同组治疗前后比较差异有统计学意义(P0.05);治疗后,治疗组VAS评分、Ca、ALP水平和24 h尿HOP低于对照组,股骨颈BMD、HHS评分、P、BGP显著高于对照组,两组比较差异具有统计学意义(P0.05)。结论强骨胶囊联合骨瓜提取物注射液治疗骨质疏松性股骨骨折具有较好的临床疗效,可有效减轻患者疼痛,增加骨密度,促进骨折愈合,调控骨代谢平衡,具有一定的临床推广应用价值。     

阿仑膦酸钠对男性骨质疏松骨转换指标与骨量的影响

目的探讨阿仑膦酸钠(ALN)对男性骨质疏松骨转换指标与骨量的影响。方法对50例老年男性骨质疏松症给予ALN10mg/d治疗,疗程1个月。结果ALN治疗后骨转换指标[尿脱氧吡啶啉(DPD)/尿肌酐(Cr)、骨钙素(BGP)、碱性磷酸酶(ALP)]降低,DPD/Cr显著降低(P<0.01),骨密度与骨强度无降低,骨折危险度无增加。结论ALN10mg/d,短期内能有效抑制男性骨质疏松的骨转换。     

青娥丸对实验性骨质疏松代谢的调节作用

目的 :研究青娥丸对骨质疏松症 (OP)动物模型的骨代谢调节作用与作用机制。方法 :8只大鼠行假手术作为对照组 ;2 4只大鼠行去势法制作OP动物模型后分为OP组、雌二醇组和青娥丸组。检测血钙 (Ca)、血磷 (P)、血雌激素 (E)、碱性磷酸酶(ALP)、耐酒石酸盐酸性磷酸酶 (TRAP)和骨密度 (BMD)等指标。结果 :上述各项指标 ,青娥丸组与OP组的比较有显著性差异(P <0 0 5～ 0 0 1)。结论 :青娥丸治疗OP模型动物的骨质疏松效果显著     

骨疏康冲剂防治大鼠骨质疏松症的生化学研究

目的 :探讨骨疏康冲剂防治大鼠骨质疏松症的作用机制。方法 :选用 3～ 4月龄Wistar大鼠 30只 ,随机分为正常对照组、模型组、骨疏康组。给模型组和骨疏康组灌服维甲酸 ( 70mg·kg- 1·d- 1) 2周 ,同时骨疏康组灌服骨疏康冲剂 ( 8g·kg- 1·d- 1)。实验第 4周末处死大鼠 ,测血Ca、P、ALP、BGP、TRAP、尿Ca/Cr、HOP/Cr等生化指标。结果 :模型组与正常对照组比较 ,血TRAP、尿Ca/Cr、尿HOP/Cr升高 (P <0 0 5)。骨疏康组与模型组比较 ,血TRAP、尿Ca/Cr、尿HOP/Cr降低 (P <0 0 5) ,血ALP、BGP升高 (P <0 0 5)。结论 :骨疏康冲剂防治骨质疏松症的作用机制考虑与抑制骨吸收 ,促进骨形成有关。     

低相对分子质量肝素对老年大鼠骨质疏松性骨折愈合过程的影响

目的探讨低相对分子质量肝素(LMWH)对老年大鼠骨质疏松性骨折愈合过程的影响。方法老年雄性SD大鼠60只,制成左股骨骨折模型,随机分为对照组和LMWH组,LMWH组于术后即刻给予LMWH100U·kg-1·d-1,共10d。两组均在术后不同时间段取骨痂,行苏木素-伊红(HE)染色、转化生长因子(TGF)-β1免疫组织化学染色,测骨密度、血清碱性磷酸酶(ALP),12周行放射学观察。结果①组织学观察:HE染色,LMWH组软骨内成骨过程较对照组延迟;TGF-β1免疫组织化学染色,LMWH组在1、2、3和4周TGF-β1阳性表达的积分吸光度值均弱于对照组,差异有统计学意义;②骨密度:LMWH组4、8和12周骨痂骨密度均低于对照组,差异有统计学意义;③血清ALP:LMWH组低于对照组,差异有统计学意义;④放射学观察:LMWH组术后12周骨折线仍较清晰,断端骨痂连接不紧密。结论LMWH通过抑制TGF-β1的表达,延缓老年大鼠骨质疏松性骨折的愈合。     

骨代谢生化指标测定在妇科临床中的应用

目的观察骨代谢生化指标在妇女绝经前后的变化,探讨其在妇科临床中的应用价值。方法严格按照随机化原则选择绝经前后的妇女各56例,运用双能X线吸收仪测量观察者腰、髋部的骨密度(BMD),同时抽取静脉血进行骨代谢酶免疫生化指标(血骨钙素BGP、Ⅰ型前胶原羧基肽CICP、碱性磷酸酶ALP、钙Ca、磷P、及Ca/Cr和HOP/Cr比值的测定,将两组结果进行统计学分析。结果绝经后组血骨钙素低于绝经前组,差异具有统计学意义(P<0.05)、绝经后组Ⅰ型前胶原羧基肽检测结果显著高于绝经前组(P<0.01)、两组骨密度检测前后下降幅度差异无统计学意义(P>0.05)、Ca/Cr和HOP/Cr比值的测定两组间差异无统计学意义,相关性统计分析显示同组内BGP、CICP、ALP有相关性。结论表明BGP、ALP、CICP能较好地反映绝经后女性体内雌激素量下降,导致骨吸收活跃的过程,而传统上临床使用的Ca/Cr和HOP/Cr比值则不能敏感的反映出此种变化,需要进一步改进。     

降钙素治疗骨质疏松性骨痛

目的 :观察降钙素治疗骨质疏松性骨痛的疗效。方法 :经双能X线骨密度测定确诊的骨质疏松病人分为降钙素组和钙组。降钙素组 33例 (男性11例 ,女性 2 2例 ) ,予降钙素 50IU ,im ,qod ;同时予葡萄糖酸钙 1.5g ,po ,bid。钙组 4 2例 (男性 12例 ,女性 30例 ) ,予碳酸钙 1.5g ,维生素D 12 5IU ,po ,qd。 2组均治疗 0 .5a。结果 :降钙素组的骨痛缓解有效率达 92 %～ 95% ,钙组为 14%～ 36% ,组间差异有非常显著意义 (P <0 .0 1)。副作用发生率降钙素组 4 3% ,钙组为 4 2 % (P >0 .0 5)。降钙素组治疗后血骨钙蛋白 (BGP)明显升高 ,血钙、碱性磷酸酶(ALP)及尿钙 /肌酐比值 (Ca/Cr) 2组治疗前后均无明显改变。结论 :与单纯口服钙治疗相比 ,降钙素肌内注射可有效缓解骨质疏松性骨痛     

经皮椎体成形术后结合阿仑膦酸钠治疗在改善骨质疏松性椎体压缩骨折患者功能障碍中的应用

目的 探讨经皮椎体成形术(PVP术)后结合阿仑膦酸钠治疗在改善骨质疏松性椎体压缩骨折患者功能障碍中的应用价值.方法 选取2013年9月至2016年9月期间确诊治疗的骨质疏松性椎体压缩骨折患者100例,依据随机数表法随机分为结合组和常规组,每组50例,常规组患者给予常规PVP术治疗和术后饮食、运动等指导干预,结合组患者在此基础上给予70mg阿仑膦酸钠口服治疗,1次/周,采用酶联免疫吸附法(ELISA)检测血清骨钙素(BGP)、碱性磷酸酶(ALP)、尿脱氧吡啶酚(DPD),采用视觉模拟评分法(VAS)评估疼痛程度,采用Oswestry功能障碍指数问卷表(ODI)评估功能障碍程度,随访6个月,统计分析所有患者临床疗效、治疗前后血清BGP、ALP、DPD水平、Cobb角、椎体前缘高度、腰椎骨密度,以及治疗前、治疗后1、3、6个月的疼痛程度和生活质量情况.结果 结合组患者治疗有效率明显高于常规组(P＜0.05);结合组患者治疗后血清BGP水平明显高于常规组,血清ALP、DPD水平明显低于常规组,差异有统计学意义(P＜0.01);结合组患者治疗后Cobb角、椎体前缘高度、腰椎骨密度水平均明显高于常规组(P＜0.01);结合组患者治疗后1、3、6个月的VAS和ODI得分明显低于常规组(P＜0.01).结论 PVP术后结合阿仑膦酸钠治疗可有效提高骨质疏松性椎体压缩骨折患者的治疗疗效,有效改善患者的Cobb角、椎体前缘高度、腰椎骨密度及骨代谢,有利于缓解患者的疼痛症状和改善患者的功能障碍,值得临床进一步推广.     

红车轴草异黄酮对维甲酸致小鼠骨质疏松的预防作用

目的研究红车轴草异黄酮对维甲酸致小鼠骨质疏松的预防作用,并探讨其主要作用机制。方法维甲酸(90mg.kg-1)致小鼠骨质疏松模型,红车轴草异黄酮(50、100、200mg·kg-1)灌胃给药,实验过程监测体重,2周后以比色法测定血清钙、磷含量和碱性磷酸酶(ALP)、抗酒石酸酸性磷酸酶(TRAP)活性,竞争放射免疫法测定血清中骨钙素(BGP)和雌二醇(E2)含量,取股骨进行骨组织形态学观察。结果维甲酸可引起高转换型骨质疏松,红车轴草异黄酮可升高E2值,降低P、ALP、TRAP、BGP水平。结论红车轴草异黄酮对维甲酸致小鼠骨质疏松有一定的预防作用,其机制可能与其减缓雌激素水平降低,抑制骨高转换有关。     

Effects of XT-44, a phosphodiesterase 4 inhibitor, in osteoblastgenesis and osteoclastgenesis in culture and its therapeutic effects in rat osteopenia models.

We have reported that denbufylline, a phosphodiesterase 4 (PDE4) inhibitor, inhibits bone loss in Walker256/S tumor-bearing rats, suggesting therapeutic potentiality of a PDE4 inhibitor in osteopenia. In the present study, effects of a new PDE4 inhibitor, 1-n-butyl-3-n-propylxanthine (XT-44), in bone were evaluated in cell cultures and animal experiments. In rat bone marrow culture, XT-44 stimulated mineralized-nodule formation, whereas it inhibited osteoclast-like cell formation in mouse bone marrow culture. In Walker256/S-bearing rats (6-week-old female Wistar Imamichi rats), rapid decrease in bone mineral density (BMD) was prominent, and oral administration of XT-44 (0.3 mg/kg, every 2 days) inhibited the decrease in BMD. In the second animal experiment, female Wistar rats (6-week-old) were sciatic neurectomized, and XT-44 was orally administered to these rats every 2 days for 4 weeks. XT-44 administration (0.3 mg/kg) recovered BMD in these neurectomized animals. Furthermore, 19-week-old, female Wistar rats were ovariectomized (OVX), and 15 weeks after surgery, these rats were orally administered XT-44 every 2 days for 8 weeks. XT-44 treatment (1 mg/kg) increased the BMD of OVX rats. These results indicate that XT-44 could be a candidate as a therapeutic drug for treating osteopenia including osteoporosis.     

Prophylactic Effects of Propranolol versus the Standard Therapy on a New Model of Disuse Osteoporosis in Rats

Disuse by bed rest, limb immobilization, or space flight causes rapid bone loss by arresting bone formation and accelerating bone resorption. Propranolol (a non-selective β-adrenergic antagonist) has been shown to improve bone properties by increasing bone formation and decreasing bone resorption in an ovariectomy-induced rat model. However, no studies have yet compared the osteoprotective properties of propranolol with well-accepted therapeutic interventions for the treatment and prevention of immobilization/disuse osteoporosis. To clarify this, we investigated the effects of propranolol compared with zoledronic acid and alfacalcidol in a new animal model of immobilization/disuse osteoporosis. Three-month-old male Wistar rats were divided into five groups with six animals in each group: (1) immobilized (IMM) control; (2) normal control; (3) IMM + zoledronic acid (50 μg/kg, intravenous single dose); (4) IMM + alfacalcidol (0.5 μg/kg, per oral daily); (5) IMM + propranolol (0.1 mg/kg, subcutaneously 5 days/week) for 10 weeks. In groups 1 and 3–5, the right hindlimb was immobilized. At the end of treatment, the femurs were removed and tested for bone porosity, bone mechanical properties, and cortical microarchitecture. Treatment with propranolol induced greater reductions in the bone porosity of the right femur and improved the mechanical properties of the femoral mid-shaft femur in comparison to the IMM control. Moreover, treatment with propranolol also improved the microarchitecture of cortical bones when compared with the IMM control, as indicated by scanning electron microscopy. The anti-osteoporotic property of propranolol was comparable with zoledronic acid and alfacalcidol. This study shows that the bone resorption induced by immobilization/disuse in rats can be suppressed by treatment with propranolol.     

特乐定治疗雄性骨质疏松大鼠的实验研究

目的：探讨特乐定对男性骨质疏松骨代谢的影响。方法：采用15周龋雄性大鼠去睾后作为动物模型，随机分为正常对照组，模型组，特乐定治疗组，28周后行血尿生化，骨密度，骨生物力学及病理检查。结果：与正常组比较，模型组睾酮水平，碱性磷酸酶，全身及股骨中点骨密度，股骨最大受力负荷及股骨最大挠度，骨小梁体积，骨表面面积／体积比，平均骨小梁厚度均明显下降，24小时尿羟脯氨酸，尿钙与肌苷比值显著增高，应用特乐定治疗后，上述指标仅有一定限度好转。结论：雄性大鼠去睾28周后形成了骨质疏松，早期应用特乐定预防治疗可使部分指标好转，但不能完全逆转骨质疏松的发生。     

女贞子治疗去卵巢大鼠骨质疏松的实验研究

目的观察女贞子对去卵巢(ovariectomy,OVX)大鼠骨质疏松(osteoporosis,OP)的治疗作用,并探讨其作用机制。方法大鼠骨质疏松模型,女贞子(9、4.5、2.25 g.kg-1.d-1)灌胃给药,实验过程称体重,连续给药26周后测定血钙(S-Ca)、血磷(S-P)、尿钙(U-Ca)、尿磷(U-P)的含量,ELISA试剂盒双抗体夹心法测定血清碱性磷酸酶(ALP)、血清骨特异性碱性磷酸酶(BALP)含量、骨钙素(OCN)含量、尿液中脱氧吡啶啉(DPD)含量,DEXA型骨密度仪分析大鼠的股骨、胫骨、第4椎骨的BMD(bone mineral density),动物处死后完整取下心、肝、脾、肺、肾、胸腺、脑、子宫进行称重,采用HE染色法进行子宫病理学检查。结果女贞子能有效抑制去卵巢所致的大鼠体重增加、升高S-Ca、S-P、降低U-Ca、U-P、降低ALP、BALP、OCN、DPD的含量,增加大鼠股骨、胫骨、第4椎骨的BMD,并且长期用药对子宫无明显刺激作用。结论女贞子对OVX大鼠所致的骨质疏松症有良好的治疗效果,其作用机制可能与其能降低高的骨转换率有关。     

Effect of Bixieqianggupian on experimental osteoporosis in rats

Objective To search the effects of Bixieqianggupian(BXQBP)on osteoporosis.Methods The experimental models of osteoporosis(OP)induced by ovariectomy(OVX),retinoic acid(RA)and dexamethasone(DXM)in rats were introduced in this study.In the same time,the influence on tibia fracture healing in rats was also observed.Moreover,the anti-inflammation effects and analgesia of BXQBP in mice and rats were also studied.Results The body weight gain induced by OVX was prevented obviously by administering BXQBP.And serum estradiol and bone gla protein(BGP)were examined by RIA,and results showed that estradiol increased and BGP decreased.Bone mineral density(BMD),bone mineral content(BMC)and bone mass of femur had increased,moreover,calcium content of bone(monitored by atomic absorption)had been improved significantly after BXQBP administration.Furthermore,biomechanical characters of bone were measured by three point bending test,and the anti-bend intensity and maximum bend strength increased remarkably.The alkaline phosphatese(ALP)decreased.And amount of urine calcium(Ca)and hydroxyproline(HOP)decreased obviously.However,effect on the proliferation of endometria was not obvious.The RA induced OP model.Compared with model,the BMD and BMC increased markedly in BXQBP rats(i.g.30 days).And bone mass and calcium content were increased.Then BGP and ALP decreased by administering BXQBP.The anti-band intensity and maximum bend strength increased evidently.And ejection of urine Ca and HOP decreased obviously.The bone trabecula became thinner,and arranged in disorder in OP rats,however,the status was reversed obviously by administrating BXQBP.The OP model also induced by DXM in rats:Effect against weight losing caused by DXM was observed in groups of three doses(i.g.12 weeks)of BXQBP.And BMD,BMC,bone mass and calcium content increased evidently.The results showed that the fracture healing had been enhanced obviously at three doses(i.g.40 days),callus growth was promoted and bone rigidity was reinforced.Moreover,BXQBP had the anti-inflammation and analgesia effects in mice and rats.Conclusions These results indicated that BXQBP had an obviously protective effect on osteoporosis in experimental animals,and promoted the fracture healing.     

骨质疏松症破骨细胞的形成与骨吸收活性的研究

目的 分析骨质疏松症骨髓单核细胞向破骨细胞转化及其骨吸收活性的变化。了解骨质疏松骨量丢失的发生机理。方法 分离、诱导培养骨质疏松症骨髓单核细胞，观察细胞的生长与分化状况，测定培养早期的细胞分泌细胞因子的水平，以抗酒石酸酸性磷酸酶（TRAP）染色和噬骨试验检测破骨细胞的形成率及其骨吸收活性，结果 在地塞米松和维生素-D3（1，25-OH2D3）的诱导下，骨髓单核细胞可向多核巨细胞转化，并呈现TRAP阳性反应及明显的噬骨性，骨质疏松症组单核细胞早期可高水平分泌白细胞介素1（IL-1β），白细胞介素6（IL-6），随之发生的TRAP阳性细胞转化率和骨吸收活性高于非骨质疏松对照组。结论 骨髓单核细胞向破骨细胞转化及其骨吸收活性的增强，是骨质疏松骨量丢失的原因之一，因单核细胞异常高水平产生的IL-1β和IL-6在其中起介导作用。     

Genistein prevents bone resorption diseases by inhibiting bone resorption and stimulating bone formation

Genistein, a soybean-derived isoflavone, has been shown to suppress osteoclastic bone resorption. To clarify the mechanisms underlying this action, we investigated the effects of genistein on the differentiation, cytoskeleton and function in mice osteoclasts in vitro and bone metabolism in ovariectomized rats. Study design: Primary OCs were isolated from 3 week-old mice and induced by 1,25(OH)(2)D(3). Then OCs were exposed to genistein at various concentration of 0 M, 10(-9) M, 10(-8) M, 10(-7) M, 10(-6) M, and 10(-5) M. The number of TRAP+ cells were counted as well as the surface area of bone resorption on bone slice. F-actin change was observed by Confocal. In vivo, forty 12 week-old female SD rats were randomly assigned to four groups: (1) sham operated (Sham); (2) (OVX); (3) ovariectomized and treated with estradiol (OVX-E); (4) ovariectomized and received genistein (OVX-G). After 12 weeks, BMD, body weight, serum level of alkaline phosphatase (ALP), acid phosphatase (ACP), osteocalcin (OC), IL-1beta, TNFalpha, IL-6 and calcitonin (CT) were evaluated. Femur were sectioned. In addition, the serum estradiol, the weight of uteri and histological behavior were also examined to indicate the side effect of genistein to the uteri. Results: In vitro, the number of TRAP+ cells decreased depending on the concentration of genistein as well as the area of bone resorption. F-actin became disorder under Confocal. In vivo, after treated with genistein, BMD and the serum level of ALP, ACP, osteocalcin increased significantly, while the serum level of IL-1beta and TNFalpha decreased. Especially, the increase of ALP and osteocalcin of OVX-G was higher than that of OVX-E. Histologically, the pachy-trabecula were observed as well as the more mineral deposition lines. Additionally, the uterus weight index and the serum estradiol in OVX-G rats were lower significantly than those of OVX-E. The epithelia of uteri gland in OVX-G appeared cubic while those of OVX-E became squamous. Conclusions: Genistein can prevent bone resorption diseases by the promotion of bone formation and the prevention of bone resorption with slight side effect.     

卵巢切除大鼠骨组织中细胞因子含量的改变及补肾中药对其的影响

目的观察卵巢切除大鼠骨组织中白细胞介素(IL)-1、IL-6和肿瘤坏死因子(TNF)-α的含量改变及补肾中药的调节作用。方法建立双侧卵巢切除(OVX)大鼠骨质疏松模型,去卵巢术后1周,用灌胃法给服补肾中药10周,以尼尔雌醇和生理盐水作为对照,观察各组大鼠骨密度及骨形态学的改变,并通过放射免疫法(RIA)检测各组大鼠骨组织中细胞因子IL-1β、IL-6和TNF-α的含量。结果①去势组较对照组骨密度显著下降(P<0.01),骨小梁稀疏断裂,骨组织中IL-1β、IL-6、TNF-α含量均显著增高(P<0.01)。②中药组骨密度显著高于去卵巢组(P<0.01),骨形态学亦显著改善。而骨组织中IL-1β、IL-6及TNF-α含量均显著低于去卵巢组(P<0.05)。结论去卵巢后大鼠骨组织中IL-1β、IL-6及TNF-α含量显著增加,而骨密度显著降低。补肾中药能较好地预防去卵巢所致大鼠的骨质疏松,其作用机制可能是其能有效地抑制去卵巢大鼠骨组织微环境中细胞因子IL-1β、IL-6和TNF-α的含量而减少骨丢失。     

Studies on the degenerative and regenerative phenomena occurring after transection and repair of the sciatic nerve in rats: effects of acetyl-L-carnitine

The effects of acetyl-L-carnitine on some degenerative and regenerative phenomena following sciatic nerve transection in rats, were studied. In Experiment 1, acetyl-L-carnitine was administered intraperitoneally at the dose of 50 mg/kg/day for 28 and 56 days following transection and microsurgical repair of the sciatic nerve. On day 56, the acetyl-L-carnitine-treated rats showed a significantly (p less than 0.05) better motor recovery ("clinical assessment") of the peroneal component of the sciatic nerve than the control rats. Twenty-eight days after nerve repair, the acetyl-L-carnitine-treated rats showed a significantly higher (p less than 0.05) number of myelinated axons in the postlesional nerve stump than control rats. Finally, the treated rats had a significantly lower (p less than 0.05) presence of atrophic fibres in the extensor digitorum longus muscle. In Experiment 2 the sciatic nerve was cut. To prevent spontaneous regeneration, a metallic clip was applied to the distal nerve stump and then the nerve stumps were positioned in different anatomical compartments. After surgery, a group of rats was treated with acetyl-L-carnitine dissolved in the drinking water (75 mg/kg/day). Another group of rats received normal water and served as the control group. Three, 6, 9, 12 and 18 months postoperatively, in the rats of both groups, the proximal sciatic nerve stump was injected with horseradish peroxidase to label the spinal cord neurons of the sciatic nerve nucleus. While in untreated rats the number of horseradish peroxidase-labelled neurons decreased with the increase in denervation time, in acetyl-L-carnitine-treated rats the number of horseradish peroxidase-labelled neurons remained stable for as long as 12 months of denervation and decreased only after 18 months of denervation. Furthermore, acetyl-L-carnitine-treated rats showed a significantly higher (p less than 0.05) number of horseradish peroxidase-labelled neurons with respect to untreated rats both after 9 and 12 months of denervation. In Experiment 3, the sciatic nerve was cut and then repaired after periods of 3, 6, 9, 12, and 18 months. Four months after nerve repair, the sciatic nerve was again cut and the proximal nerve stump was injected with horseradish peroxidase to label the spinal cord neurons of the sciatic nerve nucleus. Both acetyl-L-carnitine-treated and untreated rats showed a tendency to have an increased number of horseradish peroxidase-labelled neurons with respect to intact rats of correspondent ages.(ABSTRACT TRUNCATED AT 400 WORDS)