鼠下颌骨成骨细胞对米诺环素摄取的实验观察

目的 通过观察体外培养的成年大鼠下颌骨成骨细胞(mature rat mandibular osteoblasts,MRMOB)是否摄取米诺环素及其摄取量,为人工种植牙全身给药提供实验依据.方法 将100 mg/L的米诺环素与成骨细胞分别培养15、30、45、60 min,测定米诺环素在成骨细胞内的含量.结果 在含米诺环素的培养基中培养15、30、45、60 min后成骨细胞内米诺环素的含量分别为(17.29±1.49)、(16.87±1.57)、(16.96±1.67)和(17.94±1.63)mg/g,差异无统计学意义(P＞0.05).结论 体外培养的成年大鼠下颌骨成骨细胞能摄取米诺环素,且培养15 min以后成骨细胞内米诺环素的含量无时间依赖性.     

盐酸米诺环素对牙周袋内硫化物水平的影响

目的评价口臭的牙周炎患者局部应用盐酸米诺环素软膏对牙周袋内硫化物水平的影响。方法对15例以口臭为主诉的慢性牙周炎患者采用分口（split-mouth）设计,同一患者的一侧半口随机采用刮治和根面平整术（scaling and root planing,SRP）,另一侧采用SRP辅助用盐酸米诺环素软膏治疗。基线、治疗后6周、3个月时检查牙周袋内硫化物（sulfide in periodontal pockets,pS）水平、探诊深度（probing depth,PD）、临床附着水平（clinical attachment level,CAL）、出血指数（bleeding index,BI）、菌斑指数（plaque index,PLI）,在基线、治疗后6周刚果红涂片进行龈下微生物计数。结果在治疗后6周、3个月,SRP＋米诺环素组与单纯SRP组的各项临床指标均较治疗前明显改善（P〈0.05）;比较两组间pS值、PD、CAL、PLI、BI、龈下螺旋体比例,差异均无统计学意义。结论对于口臭的牙周炎的患者,盐酸米诺环素辅助SRP较单纯的SRP并未显示很大的优势;牙周治疗可持续3个月降低袋内硫化物水平。     

Minocycline attenuates ischemia-induced ventricular arrhythmias in rats

Minocycline has been shown to protect against myocardial ischemia–reperfusion injury. This study investigated the effects of minocycline on ischemia-induced ventricular arrhythmias in rats. Anesthetized male rats were once treated with minocycline (45 mg/kg, i.p.) 1 h before ischemia in the absence and/or presence of 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002, 0.3 mg/kg, i.v., a PI3K inhibitor) and 5-hydroxydecanoic acid [5-HD, 10 mg/kg, i.v., a specific inhibitor of mitochondrial ATP-sensitive potassium (K_ATP) channels] which were once injected 10 min before ischemia and then subjected to ischemia for 30 min. Ventricular arrhythmias were assessed. L-type Ca²⁺ current was measured by the patch-clamp technique. During the 30-minute ischemia, minocycline significantly reduced the incidence of ventricular fibrillation (VF) (P < 0.05). The duration of VT + VF, the number of VT + VF episodes and the severity of arrhythmias were all significantly reduced by minocycline compared to those in myocardial ischemia group (P < 0.05 for all). Administration of LY294002 or 5-HD abolished the protective effects of minocycline on VF incidence, the duration of VT + VF, the number of VT + VF episodes and the severity of arrhythmias (P < 0.05 for all). In addition, minocycline inhibited L-type Ca²⁺ currents of normal myocardial cell membrane in a dose-dependent manner. This study suggested that minocycline could attenuate ischemia-induced ventricular arrhythmias in rats in which PI3K/Akt signaling pathway, mitochondrial K_ATP channels and L-type Ca²⁺ channels may be involved_.     

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.     

米诺环素对实验性自身免疫性脑脊髓炎大鼠轴索损伤的影响

目的:探讨米诺环素对实验性自身免疫性脑脊髓炎(EAE)大鼠轴索损伤的影响。方法:以豚鼠全脊髓匀浆(GPSCH)免疫大鼠建立EAE模型。治疗组给予米诺环素而对照组和模型组给予生理盐水灌胃;免疫组化检测β-淀粉样前体蛋白(β-App)的表达。结果:细胞数,脊髓模型组高于治疗组而对照组最低(P<0.05),大脑和脑干模型组高于对照组(P<0.05);平均光密度,脊髓模型组高于另两组(P<0.05),大脑和脑干模型组高于治疗组而对照组最低(P<0.05)。结论:米诺环素可以抑制β-App的表达,可能对EAE轴索损伤有一定保护作用。     

米诺环素对帕金森病模型大鼠胶质细胞源性神经营养因子家族的影响

BACKGROUND:Researches have found that minocycline plays a neuroprotective effect by inhibiting the microglia cell proliferation and activation and suppressing glial cells to release cytokines and chemokines. OBJECTIVE:To investigate the influence of minocycline on glial cell line derived neurotrophic factor, NTN and gene expression in substantia nigra and corpus striatum in Parkinson’s disease model rats. METHODS:144 rats were randomly divided into four groups, with 36 rats in each group. In the normal control group, no intervention was given. In the model and experimental groups, 6-hydroxydopamine was injected in the right substantia nigra pars compacta and ventral tegmental area to establish Parkinson’s disease models. In the sham surgery group, vitamin C was injected in the two points. In the experimental group, after model establishment, rats were intragastrically given 4.5 g/L minocycline 45 mg/kg. From then on, additional 22.5 mg/kg minocycline was added every 12 hours. The last group was normal control group. Immediately, 12 hours, 1, 7, 14 and 21 days after model induction, SP immunohistochemistry was used to detect the expression of glial cell line derived neurotrophic factor and NTN expression in the substantia nigra and corpus striatum. RT-PCR was used to identify glial cell line derived neurotrophic factor and NTN mRNA expression in the substantia nigra and corpus striatum. RESULTS AND CONCLUSION:Both in the substantia nigra and corpus striatum, the positive cell number and relative gene expression of glial cell line derived neurotrophic factor and NTN were lower in the model group than in the normal control and sham surgery groups (P < 0.05). Glial cell line derived neurotrophic factor- and NTN-positive cell number and relative expression were higher in the experimental group than in the model group (P < 0.05). These findings suggest that minocycline can delay the process of Parkinson’s disease pathogenesis by promoting glial cell line derived neurotrophic factor protein and gene expression.     

Minocycline and intracerebral hemorrhage: influence of injury severity and delay to treatment

Intracerebral hemorrhage (ICH) is a devastating condition currently lacking a defined line of treatment. The inflammatory response that ensues following its onset is thought to contribute to secondary injury following ICH, making inflammation a potential therapeutic target. Minocycline (MC), a commonly used antibiotic that also has anti-inflammatory and anti-apoptotic properties, provides histological protection in several animal stroke models when given soon after injury. However, its ability to provide protection with more clinically relevant delays is unknown. The objective of this study was to examine the effects of MC on histopathological changes and long-term functional outcomes in a collagenase-induced ICH model in rats when drug administration was delayed 3 h following the onset of ICH. In accordance with other studies, MC suppressed microglial/macrophage activation in the peri-infarct region at 5 days based on B4 isolectin histochemistry. However, no reduction in infarct volume was detected at 5 or 28 days post-ICH. Minocycline given for either 5 or 14 days also provided no functional benefit as assessed with a battery of sensory-motor tests (i.e., staircase, cylinder, ladder tests). These findings raise questions about the ability of MC to provide protection in ICH when delay to treatment is increased.     

米诺环素对人牙周韧带细胞矿化能力的影响

目的探讨米诺环素对人牙周韧带细胞(periodontal ligament cells，PDLCs)碱性磷酸酶(alkaline phosphatase，ALP)活性及矿化结节形成能力的影响。方法将不同浓度的米诺环素(0，1，5，20，100，200mg／L)加入体外培养的第4代HPDLCs中，孵育4天后，检测其对细胞ALP活性的影响；将第4代的PDLCs在体外进行长期培养，实验组加入矿化液和米诺环素(20mg／L或100mg／L)，对照组只加矿化液。28天后用茜素红与VonKossa染色检测矿化结节的形成。结果20mg／L和100mg／L的米诺环素能显提高PDLCs的ALP活性．其中20mg／L具有最大的促进效应，对体外矿化结节的形成，亦有一定程度的促进作用。结论米诺环素有促进牙周韧带细胞向成骨细胞方向转化的趋势，从而有助于牙周新附着的形成。     

康复新液联合米诺环素软膏治疗慢性牙周炎的临床研究

目的探讨康复新液联合米诺环素软膏治疗慢性牙周炎的临床疗效。方法选取2013年8月—2015年8月三亚市人民医院收治的慢性牙周炎患者90例,患牙共计106颗,采用随机数字表法分为对照组和治疗组,每组各45例、患牙53颗。对照组给予盐酸米诺软膏,将其注入牙周袋中直至充满,1次/周;治疗组在对照组基础上给予康复新液,约10 m L含漱5 min左右,4次/d。两组患者均治疗4周。观察两组的临床疗效,比较两组C反应蛋白(CRP)、白细胞介素-6(IL-6)、龈沟出血指数(SBI)、牙周附着水平(AL)、菌斑指数(PLI)和牙周袋深度(PD)变化情况。结果治疗后,对照组和治疗组的总有效率分别为79.25%、96.23%,两组比较差异有统计学意义(P0.05)。治疗后,对照组SBI、AL、PLI和PD显著降低,治疗组CRP、SBI、AL、PLI和PD显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标的降低程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。结论康复新液联合米诺环素软膏治疗慢性牙周炎具有较好的临床疗效,能改善临床症状,缓解炎症反应,具有一定的临床推广应用。