依达拉奉辅助亚低温对重型颅脑创伤的血清细胞因子及凝血功能的影响

目的探讨依达拉奉辅助亚低温治疗对重型颅脑创伤（TBI）患者的凝血功能及神经生长因子（NGF）、降钙素基因相关肽（CGRP）的影响。 方法选取沧州市中心医院神经外三科自2018年8月至2019年8月收治的62例重型TBI患者，按随机数字表法分为观察组（31例）和对照组（31例）。对照组患者给予亚低温治疗，观察组患者在亚低温治疗基础上给予依达拉奉辅助治疗14 d。比较2组患者的神经功能缺损评分和疗效，观察治疗前后患者的脑内凝血功能以及血清内NGF、CGRP含量的变化。 结果观察组患者的临床治疗有效率显著高于对照组（P<0.05）。观察组患者采用依达拉奉辅助亚低温治疗后颅内水肿面积显著降低，大脑中动脉平均血流速度明显升高，美国国立卫生研究院卒中量表评分水平显著下降，巴塞尔指数评定量表评分和GCS评分显著增高，差异有统计学意义（P<0.05）。观察组患者采用依达拉奉辅助亚低温治疗后NGF、CGRP水平明显升高，血浆D-二聚体、纤维蛋白原、凝血酶原时间、凝血酶原时间国际标准比值、活化部分凝血活酶时间、凝血酶时间显著下降，抗凝血酶显著上升，差异均有统计学意义（P<0.05）。 结论依达拉奉辅助亚低温治疗重型TBI的临床治疗效果较好，安全性较高，可有效恢复患者的凝血功能，促进NGF、CGRP表达。     

循经针刺对偏头痛的即刻疗效及其机制探讨

目的:观察循经针刺治疗偏头痛患者的即可疗效,并通过检测降钙素基因相关肽(CGRP)、血浆内皮素(ET)和五羟色胺(5-HT)的表达情况探讨其机制。方法:选取2017年2月至2018年2月天津中医药大学附属武清中医院收治的偏头痛患者85例作为研究对象,根据随机数字表法将患者分为观察组(n=43)和对照组(n=40),排除不良反应的5例,2组均为40例,观察组予以循经针刺法针刺少阳经的角孙、风池、外关、阳陵泉和丘墟穴,对照组予以非经非穴治疗。于治疗前及治疗后0. 5、1、2和4 h进行偏头痛积分和VAS(视觉模拟量表评分)评估;采用放射免疫法检测降钙素基因相关肽(CGRP)和血浆内皮素(ET),利用ELISA(酶联免疫吸附剂测定)检测五羟色胺(5-HT),观察2组患者治疗前和治疗后4 h的表达情况,探讨循经针刺的疗效机制。记录研究过程中存在的不良反应。结果:1)观察组循经针刺对偏头痛的临床有效率是90. 00%,对照组是67. 50%,观察组的临床有效率优于对照组,2组比较差异有统计学意义(P 0. 05)。2) 2组治疗后0. 5、1、2和4 h的偏头痛积分和VAS评分均较治疗前下降(P 0. 05),仅治疗后2 h及治疗后4 h的偏头痛积分和VAS评分较对照组低(P 0. 05)。3) 2组治疗前CGRP和ET的表达差异无统计学意义(P 0. 05);与治疗前比较,2组治疗4 h后均可下调CGRP和ET的表达水平(P 0. 05);观察组治疗后CGRP和ET的下调水平优于对照组(P 0. 05)。4) 2组治疗前5-HT的表达无比较,差异统计学异议(P 0. 05);与治疗前比较,2组治疗4 h后均上调5-HT的表达水平(P 0. 05),其中观察组优于对照组(P 0. 05)。5)研究过程中5例患者出现不良反应,其中观察组出现3例(晕针2例+局部出血1例),对照组2例(晕针1例+局部出血1例)。晕针患者平卧取针后即可恢复,局部出血则以局部按压进行止血处理。整个研究过程中均未出现严重不良反应。结论:循经针刺治疗偏头痛患者的即刻疗效于治疗后0. 5 h症状开始缓解,于治疗后4 h疗效最佳,其即刻疗效可能与上调CGRP和5-HT表达水平和下调ET表达水平有关。     

Evaluation of the efficacy of salmon calcitonin nasal spray on bone healing following open reduction and internal fixation of mandibular fractures — A randomized controlled trial

The objective of this study was to assess the efficacy of calcitonin spray on bone healing following open reduction internal fixation (ORIF) of mandibular fractures. Fourteen patients were subdivided into a study group and a control group. A standardized surgical protocol for ORIF was followed. Postoperatively, salmon calcitonin nasal spray was administered to only the study group. The outcome parameters assessed were serum osteocalcin, pain, and radiographic bone healing. Serum osteocalcin was assessed pre- and postoperatively. Postoperative pain was documented using a visual analogue scale (VAS) on the 7th, 14th, 23rd, and 30th days. An orthopantomogram was used to score fracture healing at four time intervals, as follows: 1 — absence of callus; 2 — presence of minimal callus; 3 — considerable callus; and 4 — complete fusion of fracture. Pain scores were lower for the study group, with no pain from the fifth day, while the control group produced a mean score for day 5 of 2.43 ± 0.98 (p = 0.001). Mean postoperative serum osteocalcin levels were higher for the study group (67.82 ± 8.89) compared with the control group (57.69 ± 6.22; p = 0.029). Bone healing at 12 weeks postoperatively was level 4 for 28.6% of patients in the study group and level 3 for 71.4%. In comparison, 85.7% in the control group demonstrated level 3 healing, while 14.3% remained at level 2 (p = 0.462). Within the limitations of the study, it can be concluded that intranasal salmon calcitonin spray reduces postoperative pain and facilitates fracture healing, although its economic efficiency is still to be proven.     

Modification at Lys24 with fatty acid generates active calcitonin gene-related peptide with much improved plasma stability

As a 37-amino acid vasoactive neuropeptide, calcitonin gene-related peptide (CGRP) is widely distributed in nervous systems. The studies and clinical applications of CGRP are limited by its peptide nature and short half-life. A series of peptide analogues of the α-form of CGRP were synthesized. Afterwards, by using in vitro metabolic and activity studies, we prepared two high affinity analogues with significantly improved plasma stability.     

咬合重建对大鼠颞下颌关节降钙素基因相关肽表达的影响

目的研究咬合重建对大鼠颞下颌关节降钙素基因相关肽(calcitoningene-relatedpeptide,CGRP)表达的影响。方法Wistar雄性大鼠30只,随机分为3个实验组及相应的对照组,每组5只。实验组动物间断磨除右上、下颌磨牙牙冠至龈下,其中2组分别于第3周、第9周停止磨牙,任其自行萌出,恢复咬合关系。颞下颌关节切片行CGRP免疫组织化学反应(SABC法)。光镜观察拍片,用ImageProPlus5.1图像分析软件进行测定。结果与对照组比较,以SPSS10.0统计软件包进行分析。结果单侧咀嚼实验组,咀嚼侧和非咀嚼侧颞下颌关节单位面积内CGRP阳性纤维面积与对照组比较显著增加(P<0.01,P<0.05),其非咀嚼侧单位面积内CGRP阳性纤维面积显著高于咀嚼侧(P<0.05)。早期恢复咬合实验组,CGRP阳性纤维面积与对照组比较无显著差别(P>0.05),其咀嚼侧与非咀嚼侧比较亦无显著差别(P>0.05)。晚期恢复咬合实验组CGRP阳性纤维面积与对照组比较显著增加(P<0.01),其非咀嚼侧单位面积内CGRP阳性纤维面积显著高于咀嚼侧(P<0.05)。结论早期恢复咬合关系后,颞下颌关节内CGRP表达可恢复正常;晚期恢复咬合关系,CGRP表达不能恢复正常,CGRP参与了单侧咀嚼引起的颞下颌关节病的病理变化过程。     

降钙素基因相关肽与三叉神经痛发病关系的临床研究

目的 :通过研究三叉神经痛患者疼痛发作时是否有降钙素基因相关肽 (calcitoningene -relatedpeptide ,CGRP)参与 ,痛支与非痛支神经组织中CGRP含量是否有所不同 ,加深对三叉神经痛发病机理的认识。方法 :用放射免疫法检测 16例三叉神经痛患者疼痛发作时患侧颈外静脉血、肘静脉血及术后患侧颈外静脉血中CGRP含量并以 10名同年龄组健康成人颈外静脉血中的CGRP含量作为正常对照 ;用免疫组织化学法标记 16例患者痛支与非痛支神经切片中CGRP免疫反应阳性颗粒 ,定量观察痛支与非痛支神经纤维中CGRP免疫反应阳性颗粒的数量、面积、平均光密度和平均面积 ,从免疫反应阳性颗粒的数量和面积两个方面来说明痛支与非痛支神经纤维中CGRP的含量有无差异 ;结果 :疼痛发作时患侧颈外静脉血中CGRP含量显著升高 ,与肘静脉血、术后患侧颈外静脉血及健康对照组颈外静脉血中的CGRP含量相比 ,差异非常显著 (P <0 .0 1) ,而后三者相比差异均不显著 (P >0 .0 5 ) ;痛支神经纤维中CGRP免疫反应阳性颗粒的数量、面积均明显高于非痛支中CGRP免疫反应阳性颗粒 ,差异非常显著 (P <0 .0 1) ;结论 :CGRP与三叉神经痛发病关系密切 ,三叉神经痛发作时局部确有CGRP的参与 ,三叉神经痛的痛支神经过度合成和释放降钙素基因相关肽可能促进了局     

降钙素基因相关肽对人牙髓细胞的矿化影响

目的：分析降钙素基因相关肽（calcitonin gene-related peptide,CGRP)对人牙髓细胞促矿化功能的影响，探讨CGRP在牙髓炎症状态下表达量增多的生物学意义。方法：人牙髓细胞分实验组和对照组培养，实验组加入适量的CGRP。分别测定细胞的碱性磷酸酶活性、骨钙素含量、I型胶原mRNA表达量变化。结果：培养3、6、9、12、15d,5个时间点实验组比对照组细胞碱性磷酸酶活性增强、骨钙素含量增加，且有显著性差异（P＜0．01）。培养6d的实验组的细胞I型胶原mRNA表达比对照组明显高。结论：CGRP刺激牙髓细胞分化，促进矿化形成，CGRP表达增高将有助于修复性牙本质形成。     

免疫荧光法观察正畸大鼠牙髓CGRP的变化

目的:观察正畸牙齿移动不同时期大鼠牙髓组织中降钙素基因相关肽(CGRP)阳性神经纤维的变化。方法:采用冷冻切片和间接免疫荧光方法观察正畸大鼠牙髓组织CGRP阳性神经纤维的表达变化情况。结果:CGRP阳性神经纤维在大鼠牙髓组织中分布较丰富,在根髓呈粗大的束状;在冠髓呈条索状、串珠样,并在髓顶造牙本质细胞下层,成网状分布。正畸加力后3d大鼠牙髓CGRP阳性神经纤维数量开始增加;加力7d达到最高;至撤力后28d下降到正常水平。结论:CGRP阳性神经纤维参与了正畸牙齿移动大鼠牙髓组织的反应过程。     

Unilateral ligature-induced periodontitis influences the expression of neuropeptides in the ipsilateral and contralateral trigeminal ganglion in rats

OBJECTIVES: Expression of neuronal neuropeptides in inflammatory conditions is altered. The changes in expression of substance P (SP) and calcitonin gene-related peptide (CGRP) in ipsilateral and contralateral trigeminal ganglion (TG) neurons were investigated by immunohistochemistry one week after unilateral ligature-induced periodontitis in rats. DESIGN: A retrograde nerve tracer Fluorogold (FG) was applied into the gingival sulcus of the second maxillary molar to identify the neurons in TG that specifically innervate the inflamed gingivomucosa. In addition, neurons from the corresponding maxillary and the adjacent mandibular-ophthalmic regions in TG were analysed. RESULTS: Statistically significantly higher frequencies of CGRP-positive neurons, regardless of their size, were found in TG ipsilateral to the periodontitis (83% and 73% in FG-labelled and maxillary regions, respectively) than in the control group without periodontitis (52% and 42% in FG-labelled and maxillary regions, respectively). The frequency of small FG-labelled SP-positive neurons in the ipsilateral TG (60%) was significantly higher than in the control TG (25%). In the contralateral TG the frequency of CGRP-positive neurons in maxillary region (66%) was significantly higher than in the control group. Surprisingly, the number of SP-positive neurons in all regions of contralateral TG decreased when compared to control and ipsilateral TGs. CONCLUSIONS: Taken together, these results implicate a role of neurogenic component in the pathogenesis of periodontitis. The contralateral response in the TG could be mediated through the transmedian neurological pathways crossing in the trigeminal nuclear complex or through the systemic inflammatory reaction and the activation of the so called "neuro-immune axis".