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应用褪黑素拮抗剂(鲁辛朵)提高双足大鼠脊柱侧凸模型成功率的价值。

The value of applying a melatonin antagonist (Luzindole) in improving the success rate of the bipedal rat scoliosis model.

作者信息

Yang Shuo, Zheng Chaojun, Jiang Jianyuan, Lu Feizhou, Xia Xinlei, Zhu Wei, Jin Xiang, Ma Xiaosheng

机构信息

Department of Orthopedics, Huashan Hospital, Fudan University, No.12, Middle Wulumuqi Road, Shanghai, 200040, China.

Department of Orthopedics, The Fifth People's Hospital, Fudan University, No.128, Ruili Road, Shanghai, 200240, China.

出版信息

BMC Musculoskelet Disord. 2017 Apr 4;18(1):137. doi: 10.1186/s12891-017-1500-x.

Abstract

BACKGROUND

An ideal animal model has always been the key to research the pathogenesis and treatment of adolescent idiopathic scoliosis (AIS), while available methods have obvious disadvantages. The deficiency of melatonin has been proved relating to AIS. In this research, we intended to apply Luzindole, the melatonin antagonist, in bipedal rat model, for the block of combination of melatonin and its receptor, to inhibit the melatonin effect, and then to understand whether this method can effectively improve the scoliosis rate of bipedal rat model, and investigate the role of melatonin in scoliosis. To investigate the feasibility of improving the success rate of bipedal rat scoliosis model via intraperitoneal injection of melatonin antagonist (Luzindole).

METHODS

A total of 60 3-weeks-old Sprague-Dawley rats were included in this study, and were divided into 3 groups (A, B and C). Each group included 20 rats. Osteotomy of the bilateral proximal humerus and proximal tailbone was performed in group A and group B; intraperitoneal injection of Luzindole (0.2 mg/kg) was performed in group A and group C. X-rays were taken before the surgery, 1 month after the surgery, 3 months after the surgery, and 6 months after the surgery, to calculate the Cobb's angle of the spine (>10° was considered scoliosis). The weight of every rat was also measured at the same time. Rats were euthanized 6 months after surgery to determine the calmodulin level in thrombocytes.

RESULTS

The rate of scoliosis in group A (14/20) was significantly higher than those in group B (6/20) and group C (0/20) (P < 0.05). The differences in the weights of the 3 groups were non-significant; as were differences in the calmodulin level in thrombocytes.

CONCLUSION

The application of the melatonin antagonist of Luzindole can improve the success rate of the bipedal rat scoliosis model. Meanwhile, this study indicates that a decreased melatonin level is not the primary cause of scoliosis, but that it may increase the likelihood and severity of scoliosis.

摘要

背景

理想的动物模型一直是研究青少年特发性脊柱侧凸(AIS)发病机制和治疗方法的关键,但现有方法存在明显不足。褪黑素缺乏已被证明与AIS有关。在本研究中,我们打算将褪黑素拮抗剂鲁辛朵应用于双足大鼠模型,阻断褪黑素与其受体的结合,抑制褪黑素的作用,进而了解该方法是否能有效提高双足大鼠模型的脊柱侧凸发生率,并探究褪黑素在脊柱侧凸中的作用。探讨通过腹腔注射褪黑素拮抗剂(鲁辛朵)提高双足大鼠脊柱侧凸模型成功率的可行性。

方法

本研究共纳入60只3周龄的Sprague-Dawley大鼠,分为3组(A组、B组和C组),每组20只。A组和B组进行双侧肱骨近端和尾骨近端截骨术;A组和C组进行腹腔注射鲁辛朵(0.2mg/kg)。在手术前、手术后1个月、3个月和6个月拍摄X线片,计算脊柱的Cobb角(>10°视为脊柱侧凸)。同时测量每只大鼠的体重。术后6个月对大鼠实施安乐死,测定血小板中的钙调蛋白水平。

结果

A组脊柱侧凸发生率(14/20)显著高于B组(6/20)和C组(0/20)(P<0.05)。3组大鼠体重差异无统计学意义;血小板中钙调蛋白水平差异也无统计学意义。

结论

应用褪黑素拮抗剂鲁辛朵可提高双足大鼠脊柱侧凸模型的成功率。同时,本研究表明褪黑素水平降低不是脊柱侧凸的主要原因,但可能会增加脊柱侧凸的发生率和严重程度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fd2/5379722/ab43b218a29d/12891_2017_1500_Fig1_HTML.jpg

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