豚鼠甲流H1N1感染模型的建立及激素甲强龙对感染干预作用的探讨

目的建立豚鼠的甲流感染模型并评价激素甲强龙对感染的干预作用。方法将4～6周龄雌性SPF级豚鼠（200～300）g分为4组：正常对照组,模型组,甲强龙1组和甲强龙2组,除对照组外,豚鼠经乙醚麻醉后进行滴鼻接种A/California/7/2009（CA7）病毒,分别于攻毒后3 d和5 d给予激素甲强龙,大剂量3 d后1/4剂量给3 d,检测豚鼠感染的多项指标,观察期为14 d。结果成功建立了豚鼠的甲流感模型;甲强龙1组豚鼠肺部炎症减轻较模型组和甲强龙2组明显,存活率较这两组均降低,甲强龙2组肺部炎症较模型组减轻,而较甲强龙1组重,豚鼠的存活率较这两组均无差异。结论豚鼠能感染A/California/7/2009（CA7）病毒,感染后5 d比感染后3 d开始给予激素的干预效果好。     

Methylprednisolone and Indomethacin Inhibit Oxidative Stress Mediated Apoptosis in Rat C6 Glioblastoma Cells

Glioblastoma patients receive anti-inflammatory agent for alleviation of vasogenic edema and pain prior to surgery, radiotherapy, and chemotherapy. Oxidative stress is an important mechanism of action of some chemotherapeutic agents in the treatment of glioblastoma. So, we examined the modulatory effects of methylprednisolone (MP, a steroidal anti-inflammatory agent) and indomethacin (IM, a non-steroidal anti-inflammatory agent) on apoptosis in rat C6 glioblastoma cells following oxidative stress with hydrogen peroxide (H₂O₂). Exposure of C6 cells to 1 mM H₂O₂ for 24 h caused significant amounts of morphological and biochemical features of apoptosis. Expressions of Bax and Bcl-2 at mRNA and protein levels were altered resulting in an increase in Bax : Bcl-2 ratio in apoptotic cells, which also exhibited overexpression of 80 kDa calpain and an increase in calpain-cleaved 145 kDa α-spectrin breakdown product. Immunofluorescent and propidium iodide labeling detected caspase-3-p20 fragment in apoptotic cells, indicating activation of caspase-3 as well. Treatment of cells with 1 μM MP or 10 μM IM alone did not induce apoptosis. Pretreatment (1 h) with either 1 μM MP or 10 μM IM significantly inhibited H₂O₂ mediated apoptosis in C6 cells. Thus, pretreatment of glioblastoma with an anti-inflammatory agent, either steroidal or non-steroidal, may compromise the action of a chemotherapeutic agent that mediates therapeutic action via oxidative stress.     

Treatments for spinal cord injury: is there hope in neurosteroids?

In this review, we describe the current therapeutic strategies to find a cure for paralysis. We use the example of DHEA, a neurosteroid normally produced in the developing neural tube, to raise the hypothesis that such a class of molecules, capable of modulating proliferation of committed neural precursors, could serve as an environmental cue in the adult injured spinal cord to promote re-population of CNS lesion with endogenous dormant precursor cells. Such mechanism may be a part of the natural response to heal the injured CNS and promote recovery of function, suggesting that neurosteroid-treatment could be a promising and novel therapeutic avenue for SCI. We will review pertinent biological activities of DHEA supporting this hypothesis, demonstrate that such activities, dependent on an intact sonic-hedgehog pathway, are responsible for the motor and bladder functional recovery observed after DHEA-treatment in the adult injured spinal cord. We will also raise the current limitations to further development of DHEA- or other neurosteroid-treatments as drug candidates, including the urgent need to further document DHEA long-term safety in CNS indications.     

不同剂量甲泼尼龙对急性百草枯中毒大鼠早期肺损伤干预研究

目的:探讨不同剂量的甲泼尼龙(Methylprednisolone,MPS)对急性百草枯(paraquat,PQ)中毒大鼠早期肺损伤的疗效。方法:采用腹腔注射20%的PQ溶液制作大鼠急性PQ中毒的模型,随机均分为五组,正常对照组(A组)、染毒组(B组)、5mg/kg甲泼尼龙干预组(C组)、15mg/kg甲泼尼龙干预组(D组)、30mg/kg甲泼尼龙干预组(E组)。分三个不同时间点(24、72、168h)处死大鼠(每组每时间点6只)。观察各时间点大体标本,组织病理、肺系数和氧合指数。结果:光镜下肺组织病理学观察,与B组比较C、D、E组大鼠肺的病理学改变,肺泡腔内出血、渗出,炎性细胞浸润、肺泡隔炎性细胞浸润相对较轻,其中以C、E组减轻最为明显。在各组相同时间点肺系数:在三个时间点的值均比B组低(P<0.05),其中E组在24h、72h时间点上与C、D组有显著差异(P<0.05)。C、D、E组与B组的氧合指数的比较各个时间点上均与B组有差异(P<0.05),三组之间相互无明显差异。结论:本实验结果显示甲泼尼龙对急性百草枯中毒大鼠的肺损伤具有保护作用,且30mg/kg甲泼尼龙组要优于5mg/kg、15mg/kg甲泼尼龙组。     

不同剂量甲强龙对行胸腔镜肺癌根治术患者免疫功能的影响

目的:评价不同剂量甲强龙对行胸腔镜肺癌根治术患者免疫功能的影响。方法:选择择期行胸腔镜肺癌根治术患者40例,美国麻醉医师学会(American Society of Anesthesiology,ASA)Ⅱ~Ⅲ级,性别不限,年龄65~85岁,采用随机数字表法分为两组(n=20):甲强龙高剂量组(M组)和甲强龙低剂量组(C组)。在麻醉诱导前30 min,M组静脉注射甲强龙1 mg·kg-1,C组静脉注射甲强龙0.5 mg·kg-1。于诱导前(T0)、术毕(T1)、术后24 h(T2)抽取外周静脉血样,采用流式细胞术测定T淋巴细胞亚群CD3~+、CD4~+、CD8~+水平,计算CD4~+/CD8~+比值。结果:与T0时比较,M组T1和T2时CD3~+水平显著降低(P0.05),CD4~+水平、CD4~+/CD8~+比值有所降低,CD8~+水平有所升高,但是差异无统计学意义(P0.05);C组T1和T2时CD3~+、CD4~+、CD8~+水平以及CD4~+/CD8~+比值差异无统计学意义(P0.05)。与C组比较,M组T1和T2时CD3~+水平降低,T2时CD8~+水平显著升高(P0.05)。结论:麻醉诱导前30min静脉注射1 mg·kg~(-1)的甲强龙对行胸腔镜肺癌根治术患者的免疫功能有一定影响,而麻醉诱导前30 min静脉注射0.5 mg·kg~(-1)的甲强龙对患者的免疫功能无明显影响。     

甲基强的松龙治疗2型糖尿病合并突发性感音神经聋的临床疗效研究

目的:观察甲基强的松龙治疗2型糖尿病合并突发性感音神经聋患者的治疗效果。方法:本研究共纳入2018年1月至2020年10月期间于深圳大学附属华南医院内分泌科、耳鼻喉科住院治疗的60例合并单侧突发性感音神经聋的成人2型糖尿病患者,按照随机数字表法分为治疗组(n=30)和对照组(n=30)。两组患者均给予营养神经、胰岛素降糖和高压氧治疗,治疗组给予甲基强的松龙静脉滴注3日后,减少甲基强的松龙剂量继续治疗4天,两组总疗程为14天。观察两组患者治疗后听力障碍改善情况,两组患者分别于治疗开始前、治疗1周后、治疗2周后分别测定纯音听阈均值(PTA)、听性脑干反应(ABR)以评估治疗效果。结果:治疗2周后治疗组听力障碍分级优于对照组(P<0.05);治疗2周后,治疗组的PTA和70dB、80dB、90dB声波刺激ABR指标均优于对照组(P<0.05)。结论:甲基强的松龙联合营养神经、降糖和高压氧等综合治疗,可有效提高2型糖尿病合并突发性感音神经聋患者的听力,值得临床推广应用。     

体外修饰树突状细胞诱导免疫耐受的研究

目的:探讨体外联合应用白细胞介素10(interleukin 10,IL-10)和甲基强的松龙(methylprednisolone,Medron)修饰供体树突状细胞(dendritic cell,DC)对小鼠皮肤移植术后免疫耐受的诱导效果,为抗移植术后免疫排斥反应治疗提供依据。方法:以健康成年C57BL/6小鼠为供体。BALB/c小鼠为受体,随机分为6组。除A组外,其余各组均于皮肤移植前3d自尾静脉输入对应的供体DC。具体对应关系如下:A组为空白对照,尾静脉输入生理盐水;B组为输入未修饰的DC;C组为20μg/L IL-10处理组;D组为10mg/L Medron处理组:E组为20μg/L IL-10 10mg/L Medron处理组。同时设立F组,为BALB/c对BALB/c的同种同基因皮片移植。各组行皮肤移植术,观察受体移植皮片存活情况。结果:E组的移植皮片存活时间最长,与其它各处理组相比P＜0．05,存在统计学差异。结论:用IL-10和甲强龙修饰的供体树突状细胞对受体进行预处理,可明显延长移植皮片的存活时间。     

Effects of Methylprednisolone and Hyperbaric Oxygen on Oxidative Status after Experimental Spinal Cord Injury: A Comparative Study in Rats

The effects of hyperbaric oxygen (HBO) therapy or methylprednisolone on the oxidative status were evaluated in experimental spinal cord injury. Clip compression method was used to produce acute spinal cord injury rats. Hyperbaric oxygen was administered twice daily for a total of eight 90 min-sessions at 2.8 atmospheres. Methylprednisolone was first injected with a bolus of 30 mg/kg followed with an infusion rate of 5.4 mg/kg/h for 24 h. Five days after clip application animals were sacrificed and their traumatized spinal cord segment were excised. Tissue levels of thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were evaluated to reflect oxidant/antioxidant status. Non-treated clip-operated animals reflected significantly higher SOD, GSH-Px and TBARS levels that were found to be significantly higher than the sham-operated. Methylprednisolone was not able to lower these levels. HBO administration diminished all measured parameters significantly; however, their levels appeared already to be high when compared with sham animals. According to these results obtained on the 5th day after induction, HBO, but not methylprednisolone, seems to procure prevention against oxidative spinal cord injury.     

不同剂量甲泼尼龙三联疗法对难治性肺炎支原体肺炎患儿免疫功能及炎性因子水平的影响

目的:探讨不同剂量甲泼尼龙三联疗法对难治性肺炎支原体肺炎患儿免疫功能及炎性因子水平的影响。方法:选取我院在2017年5月到2018年6月期间收治的120例肺炎支原体肺炎患儿,根据随机数字表法将其分为对照组、低剂量组、中剂量组和高剂量组,每组均为30例。对照组采用阿奇霉素联合头孢他啶进行治疗,低剂量组、中剂量组和高剂量组在对照组的基础上分别给予1 mg/(kg·d)、2 mg/(kg·d)、5 mg/(kg·d)的甲泼尼龙进行治疗。比较各组患儿的临床疗效、临床症状消失时间及不良反应发生情况,并比较各组患儿治疗前后CD3~+、CD4~+、CD8~+、红细胞沉降率(ESR)、C反应蛋白(CRP)、肿瘤坏子因子-α(TNF-α)、白介素-6(IL-6)水平。结果:高剂量组的总有效率高于对照组(P0.05)。高剂量组患儿临床各项症状消失时间短于中剂量组、低剂量组和对照组(P0.05),中剂量组和低剂量组患儿临床各项症状消失时间短于对照组(P0.05)。治疗后高剂量组、中剂量组、低剂量组的CD3~+、CD4~+水平高于对照组(P0.05)。治疗后高剂量组患儿的ESR、CRP、IL-6水平低于中剂量组、低剂量组和对照组,且中剂量组和低剂量组患儿的ESR、CRP、IL-6水平低于对照组(P0.05)。各组的不良反应发生率比较无统计学差异(P0.05)。结论:甲泼尼龙三联疗法治疗难治性肺炎支原体肺炎患儿疗效确切,可提高患儿免疫功能,且高剂量的甲泼尼龙三联疗法可促进患儿的临床症状改善,更明显地降低炎性因子的水平,安全可靠。