乳铁蛋白的免疫调节作用研究进展

目的:综述乳铁蛋白的免疫调节功能及其临床应用情况。方法:以"乳铁蛋白""免疫调节""免疫细胞"等组合作为关键词,检索中国知网(CNKI)、Pub Med、Embase等数据库中1998年1月至2014年3月的相关文献,收集国内外对乳铁蛋白在宿主防御中的作用等方面的文献。结果:共得到文献136篇,有效文献35篇。乳铁蛋白主要通过下调炎性因子与促炎因子的释放,促进T细胞、B细胞、巨噬细胞的成熟与活化,与受体结合抑制炎性反应,募集免疫细胞、激活NK细胞,从而发挥免疫调节作用。在临床中,乳铁蛋白可应用于肠道疾病(如新生儿败血症和坏死性结肠炎)、呼吸系统疾病(如严重急性呼吸综合征)等的治疗。结论:乳铁蛋白具有免疫调节功能,正逐步应用于临床疾病的诊断与治疗中,具有进一步研究的价值与发展前景。     

乳铁蛋白对福尔马林致痛大鼠行为学及一氧化氮合酶表达的影响

目的通过观察鞘内注射乳铁蛋白对福尔马林致痛大鼠行为学及一氧化氮合酶（NOS）表达的影响，探讨乳铁蛋白可能的抗伤害机制。方法雄性SD大鼠80只，随机分为生理盐水组（NS组）和福尔马林组（F组）；实验组分为乳铁蛋白1ug-福尔马林组（F-R1组），乳铁蛋白10ug-福尔马林组（F—R10组）和乳铁蛋白100ug-福尔马林组（F—R100组）。五组鞘内分别给予NS 20ul，NS 20ul，乳铁蛋白1ug，乳铁蛋白10ug，乳铁蛋白100ug；10min后，除NS组大鼠组底注射NS 100ul外，其余各组均给予5％福尔马林100ul。经以上处理8只动物在福尔马林处理后30min取脊髓观察NOS的表达，另8只动物在福尔马林处理后0～1h观察行为学。结果F组的缩腿舔爪的时间和脊髓NOS表达显著长于，强于NS组；预先给予乳铁蛋白能抑制以上的作用，且呈剂量依赖性。结论乳铁蛋白明显抑制福尔马林致痛大鼠痛行为及NOS表达，可能是其产生抗伤害作用机制之一。     

卡马西平联合吗啡对慢性坐骨神经缩窄损伤模型大鼠的镇痛作用研究

目的:研究卡马西平联合吗啡对慢性坐骨神经缩窄损伤(CCI)模型大鼠的镇痛作用。方法:取大鼠行手术建立CCI模型,建模成功后随机分为模型组、卡马西平组(5mg·kg-1)、吗啡组(3mg·kg-1)和联用组(卡马西平5mg·kg-1+吗啡3mg·kg-1),每组16只,术后第8天分别注射相应药物,连续5d,同时设立假手术组进行比较,观察各组大鼠术后和给药过程中有无感染、自残等现象,检测给药前和给药第1、3、5天以及停药2d后机械缩足反射阈值(PWMT)和热辐射缩足反射潜伏期(PWL)变化。结果:所有大鼠术后和给药期间均无感染和自残等现象;与假手术组比较,模型组大鼠给药前和给药后各时间点的PWMT、PWL均明显减弱或缩短(P<0.01);与吗啡组比较,联用组大鼠给药后各时间点的PWMT、PWL均明显增强或延长(P<0.05或P<0.01);与给药前比较,联用组大鼠给药后各时间点的PWMT、PWL均明显增强或延长(P<0.01),卡马西平组和吗啡组大鼠停药2d后的PWMT、PWL均无明显变化。结论:卡马西平联合吗啡能明显减弱CCI模型大鼠的机械痛和热痛反应,延长吗啡作用时间,改善吗啡耐受。     

乳铁蛋白的抗病毒作用

乳铁蛋白（1aetoferrin，LF）是转铁蛋白家族中的一种铁结合糖蛋白，相对分子质量为70000～80000，对病原性微生物具有初级防御作用。LF广泛存在于乳汁、唾液、泪腺等外分泌物或血浆中。LF分子由一条多肽单链和两条多聚糖侧链组成，侧链与肽链上的天冬氨酸残基相连，二级结构由α-螺旋和β-折叠交替排列而成，且α-螺旋多于β-折叠。LF的多肽链折叠成两个对称的环形叶（C-叶和N-叶），每个叶包含两个结构域（C1、C2和N1、N2），每个结构域由一个包含金属结合位点的中心空穴定位。     

乳洁安胶囊的镇痛作用

目的观察乳洁安胶囊的镇痛作用。方法采用小鼠扭体法、热板法、蛋清致大鼠肿胀足组织中前列腺素E2(PGE2)含量的测定、观察乳洁安胶囊的镇痛作用。结果乳洁安胶囊中、高剂量组能明显减少醋酸致小鼠扭体反应次数,提高小鼠的痛阈值;随着剂量的增加其镇痛作用有增强的趋势,同时具有明显抑制大鼠足肿组织中PGE2产生的作用。结论乳洁安胶囊具有较好的镇痛作用。     

乳铁蛋白对去卵巢大鼠骨代谢的影响

目的观察乳铁蛋白（lactoferrin,LF）对去卵巢大鼠骨代谢及骨密度的影响,了解乳铁蛋白对骨质疏松的防治作用。方法70只3月龄清洁级SD（spraguedawley）健康雌性大鼠分为假手术组（sham）10只与去卵巢模型组（OVX）60只,去卵巢大鼠再随机分为6组：骨质疏松模型组（生理盐水2ml／（只·天）灌胃）、雌激素治疗组（0．1mg／kg·周,肌肉注射））,不同剂量的乳铁蛋白治疗组[0．01g／（kg·d）,0．1g／（kg·d）,1g／（kg·d）,2g／（kg·d）,灌胃],每亚组10只。连续治疗12周后观察大鼠骨密度的变化,取血检测大鼠的骨钙素（osteocalcin,BGP）,B胶原特殊序列（β-CrossLaps,β-CTK）等代谢情况。结果乳铁蛋白剂量依赖性的使骨密度增加,BGP水平升高,β-CTx值下降,1g／（kg·d）,2g／（kg·d）乳铁蛋自治疗组大鼠的股骨骨密度,全身骨密度都明显高于骨质疏松模型组（尸〈O．01）,骨钙素水平高于模型组（P〈O．01）,β-CTx值低于骨质疏松模型组（P〈0．01）。结论乳铁蛋白可促进骨形成,抑制骨吸收,减少去卵巢大鼠骨量丢失,对骨质疏松症有一定的防治作用。     

乳癖舒胶囊的镇痛及抑制大鼠乳腺增生的作用

目的研究乳癖舒胶囊的镇痛作用和对乳腺增生大鼠的抑制作用。方法用小鼠扭体法、甲醛法和大鼠热刺痛法研究镇痛作用;雌激素和孕激素诱导大鼠乳腺增生模型研究对乳腺增生的作用。结果乳癖舒胶囊能减少小鼠扭体次数,减少甲醛诱导的痛反应评分,降低大鼠热刺痛的痛阈。乳癖舒胶囊明显缩小乳腺增生大鼠的乳头直径,减少乳腺组织的乳腺小叶和腺泡数;降低乳腺增生大鼠的全血黏度。结论乳癖舒胶囊有镇痛和抑制乳腺增生的作用。     

乳铁蛋白对晚期早产儿贫血及神经行为发育的影响

目的：探讨乳铁蛋白对晚期早产儿贫血及其神经行为发育的影响。方法将2012年3月～2013年3月广东省妇女儿童医院儿童保健科门诊随访跟踪的晚期早产儿120例,随机分为乳铁蛋白组和铁剂组,观察两组患儿干预前后的血红蛋白、红细胞压积、网织红细胞、血清铁蛋白,并使用盖塞尔发展诊断量表评估其智能发育情况。结果矫正胎龄6月龄时,乳铁蛋白组及铁剂组婴儿的血红蛋白、红细胞压积、网织红细胞、血清铁蛋白差异无统计学意义（P＞0.05）。乳铁蛋白组及铁剂组婴儿盖泽尔5大能区差异无统计学意义。结论乳铁蛋白对预防晚期早产儿贫血与铁剂补充有类似效果。     

原子吸收分光光度法间接测定奶粉中的乳铁蛋白含量

目的:建立一种借助乳铁蛋白铁结合能力测定奶粉中乳铁蛋白的方法。方法:先通过额外加入的二价铁离子使乳铁蛋白中的铁达到饱和以获得稳定的铁含量,然后对蛋白反复醇沉和水溶以除去游离铁,再用原子吸收分光光度计测定铁含量,依据铁与蛋白含量的相互关系计算出乳铁蛋白含量。结果:该法快速准确,加样回收率超过96%,检测范围为3.5~100 mg.g-1。结论:可以用于婴儿奶粉中乳铁蛋白的测定。     

乳癖消颗粒抗炎镇痛作用实验研究

目的：：研究乳癖消颗粒的抗炎、镇痛作用。方法：采用二甲苯致小鼠耳廓肿胀实验观察乳癖消颗粒的抗炎作用。采用醋酸致小鼠扭体反应实验和小鼠热板法实验观察乳癖消颗粒的镇痛作用。结果：与空白对照组相比,乳癖消颗粒低、中、高剂量组(生药量分别为1.0、2.0和4.0 g·kg·d-1)均能显著抑制小鼠耳肿胀度(P<0.05或P<0.001),且能显著减少醋酸引起的小鼠扭体反应次数(P<0.01或P<0.001);中、高剂量组可提高小鼠热板痛阈值(P<0.05或P<0.01)。结论：乳癖消颗粒具有显著的抗炎镇痛作用。     

Antihyperalgesic effect of levetiracetam in neuropathic pain models in rats

The purpose of this study was to assess, in rats, the antinociceptive effects of levetiracetam (i.p.), a novel antiepileptic drug, in acute pain tests and in two models of human neuropathic pain. Levetiracetam and carbamazepine contrasted morphine by an absence of effect in the tail flick and hot plate tests. In normal rats, carbamazepine failed to modify the vocalisation thresholds to paw pressure whereas levetiracetam slightly increased this threshold only at the highest dose (540 mg/kg) for 30 min. In the sciatic nerve with chronic constriction injury model, the highest dose of levetiracetam (540 mg/kg) and carbamazepine (30 mg/kg) reversed the hyperalgesia. In streptozocin-induced diabetic rats, levetiracetam dose-dependently increased the vocalization threshold from 17 to 120 mg/kg reaching a similar effect as 10 mg/kg of carbamazepine. These results indicate that levetiracetam induces an antihyperalgesic effect in two models of human neuropathic pain, suggesting a therapeutic potential in neuropathic pain patients.     

Rats with chronic post-ischemia pain exhibit an analgesic sensitivity profile similar to human patients with complex regional pain syndrome--type I

Chronic post-ischemia pain was induced in anesthetized rats by placing a tourniquet at the ankle joint for 3 h, and removing it to allow reperfusion. The effectiveness of standard analgesic drugs to attenuate mechanical allodynia was assessed 2 and 7 days after ischemia/reperfusion. Only high doses of morphine, dexamethasone and pregabalin partially reduced mechanical allodynia 2 days post-ischemia/reperfusion, while other treatments (ibuprofen, acetaminophen, amitriptyline) were not effective. Furthermore, only the highest dose of pregabalin reduced mechanical allodynia 7 days post-ischemia/reperfusion. These results are consistent with findings that complex region pain syndrome-I pain is refractory to most standard analgesic treatments.     

坐骨神经慢性压迫损伤性疼痛与脊髓背角P物质关系研究

目的观察大鼠坐骨神经慢性压迫性损伤（CCI）后脊髓背角P物质表达的变化,探讨P物质在疼痛发生机制中的作用。方法SD雄性大鼠60只,随机分为：A组：CCI组（30只）;B组：对照组（30只）。术前及术后3、7、14、28 d分别测定大鼠热痛阈值、机械痛阈值和行为学评分。术后3、7、14、28d每组取4只,麻醉后用4%多聚甲醛灌注固定,取L4-6段脊髓,以备免疫组化,测定SP的变化。结果所有CCI动物从术后第3天起,出现明显的疼痛行为学改变和热痛阈值、机械痛阈值的降低,与对照组比较差异有统计学意义（P〈0.05或P〈0.01）。免疫组织化学结果表明,A组术后术侧明显高于B组（P〈0.05或P〈0.01）;A组术侧明显高于健侧（P〈0.05或P〈0.01）;而B组仅在第4天术侧高于健侧（P〈0.05）。结论慢性坐骨神经损伤后,脊髓背角SP的表达增加,而且表达增加与CCI大鼠的痛觉过敏、行为变化在时相上基本一致,说明CCI大鼠痛觉过敏与脊髓背角SP的表达增加有关。     

Post-injury repeated administrations of minocycline improve the antinociceptive effect of morphine in chronic constriction injury model of neuropathic pain in rat

It is confirmed that pharmacological attenuation of glial cells can alleviate neuropathic pain by lowering proinflammatory cytokine expression. The present study tries to confirm that post-injury administration of glia inhibitor, minocycline, can attenuate the neuropathic pain symptoms and improves the efficacy of morphine anti-nociception in chronic constriction injury (CCI). Male Wistar rats (230-270 g) underwent surgery for induction CCI model of neuropathy. For assessment of the thermal hyperalgesia and mechanical allodynia after CCI induction, morphine (2.5, 5, 7.5, 10 and 15 mg/kg; s.c.) and saline were administered on post-operative days (PODs) 0, 6 and 14. Hargreaves and Von-Frey tests were performed before and 30 min after morphine administration, respectively. The results showed significant decrease in antinociceptive effect of morphine on POD 6 compared to POD 0 only at the dose of 5 mg/kg. On the other hand, on POD 14 the antinociceptive effect of morphine (5, 7.5, 10 and 15 mg/kg) significantly decreased in comparison with POD 0. In another set of experiments, animals received minocycline (10, 20 and 40 mg/kg; i.p.) for eight days from POD 6 to 13 and then the antinociceptive effect of single dose of morphine 5 mg/kg was tested on POD 14. Behavioral tests showed that minocycline (40 mg/kg) could effectively attenuate the thermal hyperalgesia and mechanical allodynia on POD 13. Moreover, minocycline (40, 20 mg/kg) improved the anti-hyperalgesic, and minocycline (40 mg/kg) improved the anti-allodynic effects of morphine 5 mg/kg on POD 14. It seems that the reduction of antinociceptive effect of morphine after CCI may be mediated through glia activation. Modulation of glial activity by minocycline can attenuate CCI-induced neuropathic pain. It is also shown that repeated post-injury administration of minocycline improves the antinociceptive effect of morphine in neuropathic pain.     

汉防己甲素对急性切口痛大鼠的镇痛作用研究

目的探讨汉防己甲素对急性切口痛大鼠模型的镇痛作用。方法选择急性切口痛模型作为研究对象,将SD雄性大鼠30只随机分为急性疼痛组和汉防己甲素组,在术前1 d至术后6 d分别进行疼痛累积评分、热和机械痛阈测定。结果从切开后2 h-6 d急性疼痛模型组的热缩足反射潜伏期均显著低于基础值,但汉防己甲素组只有术后2 h-3 d热缩足反射潜伏期显著低于基础值（P〈0.05）,而且汉防己甲素组的热缩足反射潜伏期从切开后2 h-6 d均显著高于急性疼痛模型组（P〈0.05）。急性疼痛模型组和汉防己甲素组的50%缩足阈值在术后2 h-6 d均显著低于基础值（P〈0.05）,两组间基础阈值差异无统计学意义（P〉0.05）,但从切开后2 h-5 d,汉防己甲素组的50%缩足阈值显著高于急性疼痛模型组（P〈0.05）,术后6 d差异无统计学意义（P〉0.05）。急性疼痛模型组及汉防己甲素组的疼痛累积评分在切开后均较基础值显著增加（P〈0.05）,两组间基础值差异无统计学意义（P〉0.05）,但术后汉防己甲素组的评分低于对照组,第5、6天差异无统计学意义（P〉0.05）。结论汉防己甲素可缓解急性疼痛模型的静息痛、热及机械刺激的诱发痛,有希望成为新的术后镇痛方法。     

Anti-nociceptive synergism of morphine and gabapentin in neuropathic pain induced by chronic constriction injury

In order to detect an anti-nociceptive interaction between morphine and gabapentin, the anti-allodynic and anti-hyperalgesic effects of these drugs, administered either separately or in combination, were determined using the von Frey and acetone tests in a rat model of neuropathic pain (Bennett model). Morphine and gabapentin individually induced moderate attenuation of mechanical hyperalgesia, whereas the morphine and gabapentin combination completely decreased hyperalgesia. Morphine showed its maximal effect at 30 min post-injection in the acetone test; however, this effect gradually returned to the baseline value. Gabapentin did not produce an anti-allodynic effect, whereas the morphine and gabapentin combination completely decreased allodynia behavior at 30 min post-injection, an effect that persisted until 120 min. The area under the curve (AUC) of the anti-allodynic or anti-hyperalgesic effects produced by the combinations were significantly greater than the theoretical sum of effects produced by each drug alone or similar to the theoretical sum. The analysis of the effect, expressed as the AUC of the time course, supports the hypothesis that the combination of these drugs is useful in neuropathic pain therapy.     

Antinociceptive effect of three common analgesic drugs on peripheral neuropathy induced by paclitaxel in rats

Nowadays, there are no validated drugs to control the neuropathic pain induced by paclitaxel, one of the most effective antineoplastic drugs.The aim was to study the involvement of opioid and NMDA receptor on established paclitaxel-induced pain, testing three common analgesics drugs morphine, ketamine and methadone.Animals received four intraperitoneal (i.p.) injections on alternate days of paclitaxel (1 mg/kg). Three weeks later, animals showed a mechanical and heat allodynia/hyperalgesia. Morphine (1, 2.5, 5 and 10 mg/kg) abolished the reduction in the mechanical and thermal withdrawal thresholds in a dose dependent manner. This effect was blocked by naloxone. Only highest dose of ketamine (50 mg/kg) was able to increase the mechanical and thermal threshold and returned to basal values. Subanalgesic doses of morphine (1 mg/kg) and ketamine (12.5 mg/kg) produced an additive effect on heat hyperalgesia reaching an antinociceptive effect. This combination did not induce any change on tactile allodynia. Methadone (2.5 and 5 mg/kg) produced an analgesic effect that was completely antagonized by naloxone in both tests.Our results confirm that: the activation of opioids receptor produced analgesia; the blockade of NMDA receptors produce antinociception but at high doses with motor impairments and low doses of ketamine enhancing the effect of opioids.     

氯诺昔康对慢性疼痛大鼠脑脊液谷氨酸含量的影响

目的在大鼠慢性疼痛模型上,观察氯诺昔康对大鼠脑脊液谷氨酸含量的影响,探讨氯诺昔康治疗慢性疼痛的机制。方法制作大鼠慢性关节炎疼痛模型,腹腔内注射氯诺昔康用药2周,测定用药前后屈、伸关节疼痛试验评分疼痛评分、用高效液相色谱-异硫氰酸苯酯衍生法测定用药前后脑脊液谷氨酸含量的变化。结果（1）氯诺昔康用药2周屈、伸关节疼痛试验评分显著低于非用药组（P〈0．05）;（2）氯诺昔康用药2周脑脊液谷氨酸含量显著低于非用药组（P〈0。05）。结论氯诺昔康可治疗慢性疼痛,降低脑脊液谷氨酸合成是其治疗机制之一。     

Role of serotonin 5-HT<Subscript>1A</Subscript> and opioid receptors in the antiallodynic effect of tramadol in the chronic constriction injury model of neuropathic pain in rats

Rationale Tramadol (1RS, 2RS)-2-[(dimethylamino)-methyl]-1-(3-methoxyphenyl)-cyclohexanol) is an atypical centrally acting analgesic agent with weak opioid receptor affinity that, like some antidepressants, enhances the extraneuronal concentrations of the monoamine neurotransmitters, noradrenaline and serotonin, by interfering with their re-uptake and release mechanisms. Objectives The present study was undertaken to evaluate the potential role of 5-HT_1A receptors and opioids receptors in the analgesic effect of tramadol in neuropathic pain. With this aim, the effect of either a selective 5-HT_1A receptor antagonist (WAY-100635, N-2-[4-(2-methoxyphenyl-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexane carboxamide) or a selective 5-HT_1A receptor agonist (8-OH-DPAT, 8-hydroxy-2-(di-n-propylamine) tetralin hydrobromide) or an opioid receptor antagonist (naloxone; naloxone hydrochloride dihydrate) was investigated in combination with tramadol by means of the cold-plate test in the chronic constriction injury model in rats. Results The results showed that WAY-100635 (0.8 mg/kg) significantly enhanced the antiallodynic effect of non-effective doses of tramadol (5–10 mg/kg). In contrast, 8-OH-DPAT (0.5 mg/kg) counteracted the antiallodynic effect of an effective dose of tramadol (22 mg/kg). Naloxone (0.5 mg/kg) partially counteracted the antiallodynic effect of tramadol (22 mg/kg). Conclusions These findings suggest the involvement of opioid and 5-HT_1A receptors in the antinociceptive effect of tramadol and support the idea that the combination of tramadol with compounds having 5-HT_1A antagonist properties could be a new strategy to improve tramadol-induced analgesia in neuropathic pain.     

乳铁蛋白多肽嵌合体对泛耐药铜绿假单胞菌生物被膜形成的作用

目的研究乳铁蛋白多肽嵌合体对泛耐药铜绿假单胞菌生物被膜形成的作用。方法在泛耐药铜绿假单胞菌培养基（OD600=0.05）中分别加入乳铁蛋白多肽（LFcin、LFampin）以及乳铁蛋白多肽嵌合体（LFchimera）溶液干预;结晶紫法定量检测生物被膜;以结晶紫染色法,在光镜下观察生物被膜形态。结果乳铁蛋白多肽以及乳铁蛋白多肽嵌合体均能抑制泛耐药铜绿假单胞菌生物被膜形成（P〈0.05）,生物被膜量与多肽浓度呈负相关（P〈0.05）;乳铁蛋白多肽嵌合体的作用强于乳铁蛋白多肽及其混合物（P〈0.05）。结论乳铁蛋白多肽和乳铁蛋白多肽嵌合体,尤其是LFchimera对泛耐药铜绿假单胞菌生物被膜形成具有显著的抑制作用,有望用于泛耐药铜绿假单胞菌感染的治疗。