补骨脂盐炙前后对去卵巢大鼠的骨保护作用及其机制

目的 比较补骨脂盐炙前后对去卵巢（OVX）大鼠骨质疏松的治疗作用，并探讨其炮制机理。方法 制备大鼠骨质疏松模型，分别用补骨脂生、盐品灌胃，给药12周后称重，取子宫，测血清中钙（Ca）、磷（P）、碱性磷酸酶（ALP）、骨钙素（OC）以及雌二醇（E2）含量，测骨生物力学强度和骨密度（BMD），观察骨小梁微结构。制备补骨脂生、盐品含药血清，检测含药血清对成骨细胞增殖和分化影响。检测补骨脂生、盐品水煎液和含药血清中主要有效成分含量。结果 补骨脂生、盐品均能有效抑制去卵巢所致的大鼠体重增加和子宫萎缩，升高血清Ca、P含量，降低ALP、OC和E2含量，显著提高BMD、骨生物力学强度，改善骨小梁结构的完整性。补骨脂生、盐品对成骨细胞的增殖和分化均有明显的促进作用，且盐品效果优于生品。此外，补骨脂盐炙后有效成分的煎出和入血成分的含量存在明显差异。结论 补骨脂生、盐品对OVX所致的大鼠骨质疏松症有良好的治疗效果，并且补骨脂盐品的抗骨质疏松作用更强，这与补骨脂盐炙促进补骨脂苷、异补骨脂苷等有效成分煎出和盐炙后补骨脂素、异补骨脂素等入血有效成分增加有关。     

柴胡栀子汤联合甲巯咪唑治疗甲状腺功能亢进症的临床效果

目的观察柴胡栀子汤联合甲巯咪唑治疗甲状腺功能亢症的临床效果。方法选取2017年6月-2019年10月南通市通州区中医院收治的甲状腺功能亢进症患者80例,根据随机数字表法分为对照组(40例)单纯予以甲巯咪唑片治疗,观察组(40例)在对照组基础上联合柴胡栀子汤治疗。比较2组临床疗效,治疗前后中医证候积分、甲状腺激素[总甲状腺素(TT4)、游离甲状腺激素T3(FT3)、游离甲状腺激素T4(FT4)、促甲状腺素(TSH)]水平变化,及统计2组用药后并发症发生率。结果治疗1年后,观察组总有效率为97.50%,高于对照组的80.00%(χ²=6.135,P=0.013);2组烦热、易汗、眼球突出积分均较治疗前降低(P<0.01),且观察组各项积分低于对照组(P均<0.01);2组TT4、FT3、FT4、水平均较治疗前降低(P<0.01),TSH水平较治疗前升高(P<0.01),且观察组降低或升高幅度大于对照组(P均<0.01);观察组患者用药后并发症总发生率为5.00%,低于对照组的30.00%(χ²=8.658,P=0.003)。结论甲状腺功能亢进症采用柴胡栀子汤联合甲巯咪唑治疗效果确切,可有效改善患者病症表现及甲状腺激素水平,且安全性高,值得临床推广与应用。     

Analysis on 113 Cases of Adverse Reactions Caused by β-Lactam Antibiotics

The objectives of this study were to learn about the characteristics and rules of the occurrence of adverse reactions caused by lactam antibiotics and provide a reference for clinical drug use. Methods: A retrospective study was made to analyse the 113 case reports of adverse reactions caused by β-lactam antibiotics collected in our hospital between 2007 and 2009. Results: 113 cases of ADR involved 17 kinds of β-lactam antibiotics, headed by ceftriaxone sodium. The most common manifestation was skin and accessory damage; nervous system and gastrointestinal system damage were also easier to find, and the administration route was mainly intravenous infusion. Conclusion: The clinical application of β-lactam antibiotics should pay attention to adverse reaction monitoring and rational drug use to reduce the incidence of adverse reactions.     

清脂护肝方对大鼠非酒精性脂肪性肝炎的作用研究

目的探讨清脂护肝方对大鼠非酒精性脂肪性肝炎的作用及其机制。方法 58只雄性SD大鼠,均喂养高脂饲料,予以12只作对应。将造模成功的大鼠再随机分为模型组、低剂量、中剂量和高剂量清脂护肝方组,分别给予0.9%NaCl溶液灌胃,清脂护肝方组予清脂护肝方药液灌胃6周;观察记录大鼠的行为表现及体质量变化。干预结束后次日处死所有大鼠并留取血清和肝脏,检测清脂护肝方对NASH大鼠肝生化指标的影响。免疫组织化学方法检测NASH大鼠肝组织中SSeCKS、Hck、Lyn、Fgr的表达水平。体外实验:对库普弗细胞株采用不同浓度不同时间的CCL4刺激,用优选方案的清脂护肝方药物血清培养后检测SSeCKS、Hck、Lyn、Fgr的表达。结果与正常对照组相比,模型组大鼠体重明显增加(P0.05);模型组ALT、AST、TBIl均较正常对照组升高(P0.05);模型组TG、CH、LDL均明显上升(P0.01),HDL亦有所降低(P0.05)。与模型组相比,中大剂量清脂护肝方组体重均有减轻,其中大剂量组的体重减轻最为明显(P0.01);清脂护肝方各剂量治疗组ALT与模型组比较明显降低(P0.01),大剂量治疗组AST与模型组比较明显降低(P0.01);清脂护肝方中、大剂量组的血清TBIL较模型组显著下降(P0.01);与模型组比较,清脂护肝方组的TG、LDL有所降低(P0.05),尤其大剂量组降低相对更明显;清脂护肝方各剂量组CH有所降低,但仅有大剂量组有统计学差异(P0.05)。ICC结果表明:Lyn、Hck在kupffer细胞中有表达,并与炎症程度呈正相关,清脂护肝方药物血清培养后表达减少,Fgr和SSeCKS在kupffer细胞中无明显表达。ICC结果表明:Hck、Lyn在正常肝脏组织中低表达,模型组中高表达,用药组无论是大、中、小剂量组,在抑制Hck、Lyn两种Src相关激酶成员的阳性表达是有显著效果,特别是大剂量组,与模型组比较有显著意义(P0.01);模型组SSeCKS蛋白的表达显著低于正常组,在治疗组中的表达介于模型组和正常组,同时伴随Lyn、Hck表达的升高呈减少趋势,提示SSeCKS与Src家族相关激酶(Lyn、Hck)存在某种上下游抑制关系;而清脂护肝方对Fgr的表达无明显影响,用药前后无统计学意义(P0.05)。结论清脂护肝方能减轻肝脏的炎性反应,明显改善肝功能和血脂指标,其机制可能与SSeCKS、Lyn、Hck信号通路有关,且高剂量时疗效更优。     

Mechanical and hypoxia stress can cause chondrocytes apoptosis through over-activation of endoplasmic reticulum stress

ObjectiveTo examine the role of mechanical force and hypoxia on chondrocytes apoptosis and osteoarthritis (OA)-liked pathological change on mandibular cartilage through over-activation of endoplasmic reticulum stress (ERS).MethodsWe used two in vitro models to examine the effect of mechanical force and hypoxia on chondrocytes apoptosis separately. The mandibular condylar chondrocytes were obtained from three-week-old male Sprague–Dawley rats. Flexcell 5000T apparatus was used to produce mechanical forces (12%, 0.5 Hz, 24 h vs 20%, 0.5 Hz, 24 h) on chondrocytes. For hypoxia experiment, the concentration of O₂ was down regulated to 5% or 1%. Cell apoptosis rates were quantified by annexin V and propidium iodide (PI) double staining and FACS analysis. Quantitative real-time PCR and western blot were performed to evaluate the activation of ERS and cellular hypoxia. Then we used a mechanical stress loading rat model to verify the involvement of ERS in OA-liked mandibular cartilage pathological change. Histological changes in mandibular condylar cartilage were assessed via hematoxylin & eosin (HE) staining. Immunohistochemistry of GRP78, GRP94, HIF-1α, and HIF-2α were performed to evaluate activation of the ERS and existence of hypoxia. Apoptotic cells were detected by the TUNEL method.ResultsTunicamycin, 20% mechanical forces and hypoxia (1% O₂) all significantly increased chondrocytes apoptosis rates and expression of ERS markers (GRP78, GRP94 and Caspase 12). However, 12% mechanical forces can only increase the apoptotic sensitivity of chondrocytes. Mechanical stress resulted in OA-liked pathological change on rat mandibular condylar cartilage which included thinning cartilage and bone erosion. The number of apoptotic cells increased. ERS and hypoxia markers expressions were also enhanced. Salubrinal, an ERS inhibitor, can reverse these effects in vitro and in vivo through the down-regulation of ERS markers and hypoxia markers.ConclusionWe confirmed that mechanical stress and local hypoxia both contributed to the chondrocytes apoptosis. Mechanical stress can cause OA-like pathological change in rat mandibular condylar cartilage via ERS activation and hypoxia existed in the meantime. Both mechanical forces and hypoxia can induce ERS and cause chondrocytes apoptosis only if the stimulate was in higher level. Salubrinal can protect chondrocytes from apoptosis, and relieve OA-liked pathological change on mandibular condylar cartilage under mechanical stress stimulation.     

清脂护肝方对非酒精性脂肪肝大鼠肝组织中Hck、Lyn、Fgr、SSeCKS表达的影响

目的观察不同剂量清脂护肝方对非酒精性脂肪肝(NAFLD)大鼠肝组织中Src家族相关激酶(Hck、Lyn、Fgr)和Src抑制的蛋白激酶C底物(SSe CKS)表达的影响,探讨其治疗NAFLD的作用机制。方法 2月龄SD大鼠58只,除正常组12只大鼠外,其余大鼠均喂养高脂饲料(80.5%普通饲料、2%胆固醇、12%猪油、5%蛋黄粉、0.5%胆酸钠),8周后随机抽取6只验证非酒精性脂肪肝大鼠造模是否成功;将造模成功的大鼠再随机分为模型组,清脂护肝方高、中、低剂量组,每组10只。清脂护肝方高、中、低剂量组予相应清脂护肝方药液灌胃6周,模型组和正常组以0.9%Na Cl溶液灌胃6周。实验结束后用免疫组织化学(IHC)法检测大鼠肝组织中Hck、Lyn、Fgr、SSe CKS的表达及其相关关系。结果与正常组比较,模型组SSe CKS、Hck、Lyn表达差异均有统计学意义(P<0.01)。与模型组比较,清脂护肝高、中、低剂量组Hck、Lyn表达差异均有统计学意义(P<0.01),清脂护肝低、中剂量组SSe CKS表达差异有统计学意义(P<0.05,P<0.01)。清脂护肝方对Fgr的表达无明显影响(P>0.05)。结论清脂护肝方能够调控SSe CKS、Lyn、Hck的表达从而减轻肝脏的炎症反应,是清脂护肝方治疗非酒精性脂肪肝的机制之一。     

吴坚辨治白塞氏病经验

<正>白塞氏病又称白塞氏综合征,是一种原因不明,以小血管炎为病理基础的慢性进行性多系统疾病,其中以口腔溃疡、生殖器溃疡、皮肤及眼部损害为常见,关节、心血管、消化道、神经系统、肺、肾与附睾等均可受累。[1]常累及关节、神经系统、消化道、肺、肾以及附睾等器官——吴坚教授曾师承国医大师朱良春教授,在白塞氏病的中医临床诊治方面,积累了较为丰富的临床经验。现将吴坚教授白塞氏病辨治经验介绍如下。     

中药方对阿霉素所致大鼠心肌损伤的保护作用研究

目的研究中药方对阿霉素（ADR）所致大鼠心肌毒性的保护作用,并探讨其机制。方法将33只大鼠随机分为正常对照组、ADR模型组、中药治疗组,观察比较血清肌钙蛋白I（cTnI）、一氧化氮（NO）、超敏C-反应蛋白（hsCRP）,血浆超氧化物歧化酶（SOD）、丙二醛（MDA）、B型利钠肽（BNP）水平,以及心电图、心肌病理和超微结构的改变。结果模型组cTnI、BNP、MDA、NO、hsCRP含量明显增高,SOD活性显著降低,与正常组比较差异有统计学意义（P〈0.05）,并见心肌组织、超微结构的损伤;中药组与模型组比较,cTnI、BNP、MDA、NO、hsCRP水平明显下降（P〈0.05）,SOD活性显著升高（P〈0.05）,而与正常组比较,各值差异均无统计学意义（P〉0.05）,且心肌组织与正常组几乎接近,超微结构的损伤较模型组明显减轻。结论中药方可以预防和减轻阿霉素对心肌的毒性损伤,其机制可能与保护心肌SOD活性及清除自由基,防止脂质过氧化损伤有关。     

弯棒旋转法治疗胸腰椎骨折的基础与临床研究

目的测量正常人胸腰段生理前弯角度的范围（T11～L2）,对于胸腰段骨折的患者,利用理论值折弯棒并旋棒,观察矫形效果。方法测量50例正常人胸腰段脊柱矢状位Cobb角及30例胸腰段骨折患者的目标椎体术前、术后矢状位Cobb角。结果正常人目标脊椎Cobb角、弯棒矫形后脊椎Cobb角运用配对设计的秩和检验,得出正常人目标脊椎Cobb角与弯棒矫形后目标脊椎Cobb角差值没有统计学意义。结论测量正常人胸腰段椎体的生理前弯角度,并按照此角度作为Basis脊柱内固定系统旋棒的角度参考值,能够较好的还原骨折前此段椎体的生理弧度;同时也能获得胸腰椎矢状面的重建,因此弯棒旋棒法治疗胸腰椎骨折对恢复胸腰段脊柱正常生理弧度有良好的治疗效果。