SR-BI在OxLDL诱导人血单核细胞表达致炎细胞因子mRNA中的作用

目的　探讨SR BI在OxLDL刺激人血单核细胞表达致炎细胞因子mRNA中的作用。方法　用原位杂交方法研究OxLDL、SR A的特异性抑制性配体 Fucoidin、17β Estrogen对人血单核细胞SR BImRNA表达的影响及其与MCP 1、PDGF、bFGF、IL 10mRNA表达的关系。结果　OxLDL(10～ 30mg·L-1)能剂量依赖性刺激SR BImRNA表达 (均P <0 .0 0 1) ,Fucoidin(5 0～ 2 5 0mg·L-1)能拮抗 2 0mg·L-1OxLDL的诱导效应 (均P <0 .0 0 1) ,同MCP 1、PDGF、bFGF、IL 10四种致炎细胞因子mRNA的表达相一致。 17β Estrogen(1× 10 -9mol·L-1～ 1× 10 -5mol·L-1)抑制上述致炎细胞因子mRNA表达 (均P <0 .0 0 1) ,但剂量依赖性提高SR BImRNA表达 (P <0 .0 0 1) ;在 1× 10 -5mol·L-1时 ,OxLDL(10～ 30mg·L-1)能对抗Fucoidin(2 5mg·L-1)而刺激上述致炎细胞因子mRNA表达 (均P <0 .0 0 1)。结论　SR BI可能不参与OxLDL刺激人血单核细胞表达致炎细胞因子过程     

川芎嗪对体外培养兔关节软骨细胞MMP-1、MMP-13和TIMP-1表达的影响

目的研究川芎嗪对IL-1β诱导的兔关节软骨细胞损伤的影响。方法体外分离培养兔关节软骨细胞,并以其为实验模型;将实验分为正常对照组、白介素组、川芎嗪+白介素组;MTT法检测细胞增殖情况;Real-time PCR检测MMP-1、MMP-13和TIMP-1的mRNA表达量。结果 MTT检测结果显示,川芎嗪+白介素组细胞增殖情况显著高于正常对照组和白介素组(P<0.05);Real-time PCR结果显示,川芎嗪+白介素组MMP-1和MMP-13的mRNA表达量显著低于白介素组(P<0.05),而TIMP-1的mRNA表达量则显著高于白介素组(P<0.05)。结论川芎嗪可抑制IL-1β对软骨细胞的炎症损伤,具有保护软骨细胞,延缓软骨基质降解的作用,临床上可作为OA的治疗用药。     

关节内注射川芎嗪对兔膝关节软骨退变的影响

目的观察川芎嗪关节腔内注射对骨关节炎过程中软骨退变的保护作用,探讨川芎嗪关节腔注射治疗骨关节炎的应用前景。方法健康成熟新西兰大白兔26只,设立正常组、模型组、对照组和实验组。模型组、对照组及实验组建立骨关节炎模型。对照组与实验组分别关节腔注射地塞米松0.3 mL和川芎嗪0.3 mL。每周一次。在模型建立6周和9周时各组分别处死一半动物,去除关节炎模型,取材进行大体标本病理学观察,并经光镜和透射电镜观察膝关节软骨的病理变化。结果在6和9周时,实验组的大体标本软骨损伤分级明显优于其他3组;Mankin软骨组织学评分与上述两组相比,有非常显著性差异(P<0.01);电镜超微结构观察其病理改变明显轻于对照组和模型组。对照组大体标本软骨损伤分级与模型组基本相同;Mankin软骨组织学评分与模型组比较无显著性差异(P>0.05);电镜超微结构观察对照组与模型组在细胞形态、细胞内细胞器改变等方面相似。结论关节腔内注射川芎嗪能减轻兔膝关节炎模型的关节软骨退变程度,并可促进软骨的自身修复;激素关节腔内注射对损伤软骨的修复作用不明显。     

缓激肽在依那普利干预心肌梗塞大鼠心肌胶原代谢中的作用

目的　探讨缓激肽 (BK)对大鼠心肌梗塞 (MI)后心肌胶原生化改建的影响 ,以及血管紧张素转换酶抑制剂 (ACEI)对心肌胶原的影响是否与抑制BK的降解有关。方法　复制大鼠MI模型后 ,第 3天开始给予依那普利(5 0 0 μg·kg-1·d-1) 4周 ,测定左心室非梗塞区组织的胶原含量及Ⅰ、Ⅲ型胶原的比值 (Ⅰ /Ⅲ ) ,并与依那普利 +BKB2 受体阻断剂HOE 14 0 (5 0 0 μg·kg-1·d-1由微渗透泵给入 )组、血管紧张素ⅡⅠ型受体 (AT1)阻断剂Losartan(3mg·kg-1·d-1)组及对照组相比较。结果　依那普利、Losartan组的胶原含量及其Ⅰ /Ⅲ比值均较对照组降低(P <0 0 5 ) ,而Losartan组的胶原含量及其Ⅰ /Ⅲ比值又低于依那普利组 (P <0 0 5 ) ,依那普利 +HOE 14 0组的胶原含量及Ⅰ /Ⅲ比值较单独用依那普利组明显升高 (P <0 0 5 )。结论　BK能抑制大鼠MI后左心室胶原的生成及降低胶原Ⅰ /Ⅲ比值 ;ACEI阻抑左心室胶原生化改建的作用机制是既抑制了血管紧张素Ⅱ (AngⅡ )的生成又促使了心肌局部BK的积累。     

哇巴因对血管紧张素Ⅱ及其1型和2型受体mRNA在心肌中表达的影响

目的观察哇巴因(Ouabain)对血管紧张素Ⅱ(AngⅡ)及其1型(AT1)与2型(AT2)受体mRNA在心肌中表达的影响。方法60只SD大鼠随机分为3组,分别为Ouabain组[27.8 ng/(kg.d)Ouabain腹腔注射]、Losartan组[27.8 ng/(kg.d)Ouabain腹腔注射,同时给予Losartan 30 ng/(kg.d)灌胃]、对照组(生理盐水2 mL/d腹腔注射),每周测定鼠尾血压,共6周。应用放免法测定各组大鼠血浆及心肌中AngⅡ质量浓度,同时采用实时定量荧光PCR(FQ-PCR)观察心肌中AT1和AT2mRNA表达的变化。结果血浆中的AngⅡ质量浓度在Ouabain组及Losartan组均显著高于对照组(P<0.05),而Ouabain组心肌中AngⅡ质量浓度无明显变化。与对照组相比,Ouabain组及Losartan组心肌中AT1mRNA与AT2mRNA的表达明显上调(P<0.05)。结论外周长期、慢性给予Ouabain后可持续升高SD大鼠的血压,并使RAS系统激活,这一作用可能是通过AT1受体介导。给予Ouabain激活AT1受体的同时,AT2活性也增加。     

莫索尼定对自发性高血压大鼠左室肥厚及c-myc基因表达的影响

目的　研究国产盐酸莫索尼定 (Mox)对自发性高血压大鼠 (SHR)左室肥厚的逆转作用及其可能机制。方法　2 0周龄的雄性自发性高血压大鼠 30只随机分为①Mox +SHR组 ,②Cap +SHR组 ,③SHR组 ,每组 10只。另设性别、周龄相配的SD大鼠 10只为正常对照组 (NC组 )。观察期末 ,测量左心室重 体重 (LVW BW )、左室胶原分数(CVF)、标准化血管周胶原面积 (PVCA)、肌间动脉中膜厚度 (AMT)及左室组织c myc基因表达的变化。 结果　Mox+SHR组不仅LVW BW明显低于SHR组 [(3.4 6± 0 .13)mg·g- 1 vs(3.96± 0 .18)mg·g- 1 ,P <0 .0 1],CVF低于SHR组 [(0 .0 86± 0 .0 18)vs(0 .0 4 6± 0 .0 15 ) ,P <0 .0 1],PVCA少于SHR组 [(0 .6 9± 0 .11)vs(1.34± 0 .2 9) ,P <0 .0 1],AMT薄于SHR组 [(7.97± 0 .73) μmvs(11.91± 1.16 ) μm ,P <0 .0 1],而且c myc表达量也低于SHR组 [(0 .74±0 .16 )Avs(1.2 4± 0 .2 1)A ,P <0 .0 1]。结论　盐酸莫索尼定能够逆转自发性高血压大鼠的左室肥厚 ,对c myc基因表达的减少可能是其作用机制     

EFFECTS OF OUABAIN AND DIGOXIN ON THE GENE EXPRESSION OFSODIUM PUMP α-SUBUNIT ISOFORM IN AORTIC SMOOTH MUSCLE OF RATS

Accumulating evidence indicates that endoge-nous ligands of the digitalis receptor may exist inthe mammalian body, which has recently been de-scribed to be indistinguishable from ouabainL1'2j.Endogenous ouabain (EO) might induce many cy-tobiological changes and play an important role inregulating water and sodium metabolism and vas-cular tone in the body["'J. Many studies haveshowed that EO content in both hypertensive pa-tients and hypertensive animals is much more thanthose of normal subje…     

珍菊降压片对肾性高血压大鼠血压的影响

目的　观察珍菊降压片 (ZJ)及其西药组分对肾性高血压大鼠 (RHR)血压和停药后血压反跳的影响 ,并研究其对RHR血脂与血脂蛋白的影响。方法　左肾动脉狭窄法建立两肾一夹高血压大鼠模型 ;无创尾套法测量清醒RHR尾动脉收缩压。结果　与模型组比较 ,ZJ组 (4 0mg·kg-1,80mg·kg-1,16 0mg·kg-1)及西药组分组 (1.79mg·kg-1,相当于全药中剂量组 )对RHR有明显的降压作用 (P <0 .0 1) ;ZJ各剂量间降压作用无显著性差异 ;同比剂量组(80mg·kg-1)与西药组分组 (1.79mg·kg-1)降压作用无显著性差异 (P >0 .0 5 ) ;与西药组分组 (1.79mg·kg-1)比较 ,ZJ未出现血压反跳现象 (P <0 .0 5 ) ;ZJ对血脂和血脂蛋白无显著性影响 (P >0 .0 5 )。结论　珍菊降压片有良好的抗高血压作用 ,对血脂和血脂蛋白无显著性影响     

哇巴因、地高辛与高血压发病关系的研究

目的　观察哇巴因、地高辛对组织钠泵α亚单位基因表达的不同影响 ,探讨哇巴因与高血压发病的可能关系。方法　给予大鼠哇巴因 30 μg·kg-1·d-1,地高辛 4 0 μg·kg-1·d-1腹腔注射 7周。用免疫组化及原位杂交方法检测心脏、肾脏、肝脏、腹主动脉和肾上腺组织钠泵α亚单位蛋白水平及mRNA水平的表达。结果　哇巴因与地高辛对上述组织尤其是动脉及肾脏的钠泵α亚单位表达的影响不同 ,哇巴因增强动脉的α2 表达 ,地高辛则抑制其表达 ;哇巴因使肾脏α1表达增强 ,地高辛则使其减弱。结论　哇巴因导致组织钠泵α亚单位基因异常表达 ,这可能在高血压的发病中有重要意义     

雌激素对骨关节炎模型软骨基质蛋白多糖变化的影响

目的　观察雌激素对骨关节炎 (OA)模型软骨基质蛋白多糖变化的影响 ,探讨外源性雌激素治疗OA的作用机理。方法　以家兔制作OA动物模型 ,在雌激素干预治疗的基础上 ,获取病变早、中、晚期关节软骨 ,提取葡糖氨基聚糖 (GAG) ,用生化和放射免疫技术测定其中不同种类GAG及其功能基团的含量。结果　在病变的不同时期 ,对照组GAG的总量、透明质酸的含量均减少 ,硫酸软骨素与硫酸角质素的含量和比例增高 ;而雌激素干预组GAG的总量、透明质酸的含量、硫酸软骨素与硫酸角质素的含量和比例与正常组接近。结论　外源性雌激素通过抑制糖蛋白降解对OA提供保护作用。     

Accurate 3D reconstruction of subject-specific knee finite element model to simulate the articular cartilage defects

The biomechanical relationship between the articular cartilage defect and knee osteoarthritis (OA) has not been clearly defined. This study presents a 3D knee finite element model (FEM) to determine the effect of cartilage defects on the stress distribution around the defect rim. The complete knee FEM, which includes bones, articular cartilages, menisci and ligaments, is developed from computed tomography and magnetic resonance images. This FEM then is validated and used to simulate femoral cartilage defects. Based on the obtained results, it is confirmed that the 3D knee FEM is reconstructed with high-fidelity level and can faithfully predict the knee contact behavior. Cartilage defects drastically affect the stress distribution on articular cartilages. When the defect size was smaller than 1.00 cm², the stress elevation and redistribution were found undistinguishable. However, significant stress elevation and redistribution were detected due to the large defect sizes (⩾1.00 cm²). This alteration of stress distribution has important implications relating to the progression of cartilage defect to OA in the human knee joint.     

大剂量螺内酯对大鼠肝纤维化进展及血管紧张素Ⅱ水平的影响

目的　论证螺内酯的抗肝纤维化作用 ,动态观察其对大鼠肝纤维化进展中血管紧张素Ⅱ (AngⅡ )水平的影响。方法　 90只SD大鼠随机分为 3组 :①正常对照组 (8只 ) :正常饮水饮食 ,皮下注射纯花生油 ;②模型组 (4 2只 ) :皮下注射 4 0 % (体积分数 )四氯化碳花生油溶液 ,辅以高脂、高胆固醇、低蛋白饮食 ;③螺内酯组 (4 0只 ) :造模方法同模型组 ,并以 10 0mg·g-1·d-1剂量的螺内酯灌胃。于 2、4、6、8周末 ,后两组分别处死一批动物 ,放免法测定其血清及肝匀浆中AngⅡ水平 ,取肝脏标本做HE和VG染色观察。结果　①螺内酯组的一般状况较好 ,病理改变较模型组轻 ,胶原面积比减少 ,两者有显著差异 (P <0 .0 5 ) ;②螺内酯组和模型组大鼠血清及肝匀浆中AngⅡ水平均从第 2周开始较正常对照组显著升高 ;从第 4周开始 ,螺内酯组血清中AngⅡ水平较同期模型组显著升高 ,而肝匀浆中AngⅡ水平较同期模型组显著降低。结论　大剂量螺内酯可以部分抑制肝纤维化的进展 ,其作用机制可能与肝纤维化进展过程中肝匀浆中AngⅡ水平降低有关     

单纯疱疹病毒性角膜炎土贝母皂甙点眼的浓度筛选与刺激性评价

目的　通过动物试验评价土贝母皂甙 (tubeimoside ,Tu)治疗单纯疱疹病毒性角膜炎 (herpessimplexkeratitis ,HSK)的效果及点眼刺激性 ,并确定其点眼浓度值。方法　根据药物的眼刺激性选用 5、2、0 .8、8× 10 -2 、8× 10 -3、8× 10 -4 g·L-1Tu点眼 ,确定 0 .4、0 .2、0 .1g·L-1评价药物疗效。在地鼠肾细胞BHK 2 1上进行单纯疱疹病毒Ⅰ型(HSV 1型 )SM4 4毒株复苏 ,制作兔HSK模型。采用裂隙灯显微镜、扫描电镜和透射电镜观察眼部病变的动态变化评价Tu疗效。结果　 5、2 g·L-1Tu有中度刺激性 ,0 .8g·L-1Tu有轻度刺激性。 8× 10 -2 、8× 10 -3、8× 10 -4 g·L-13组Tu无任何眼刺激性。 0 .4g·L-1Tu有轻度刺激性 ,0 .1、0 .2 g·L-1Tu无刺激性。 0 .4、0 .2、0 .1g·L-13组Tu均具有一定疗效。结论　Tu点眼剂的浓度与刺激性呈正相关 ,点眼刺激性从轻度到无的界值浓度为 0 .4、0 .2、0 .1g·L-1。治疗实验性HSK有一定的疗效 ,但尚不及无环鸟苷     

EFFECT OF LOW SELENIUM ON CHONDROCYTE DIFFERENTIATION AND DIFFERENTIAL EXPRESSION OF COLLAGEN TYPES Ⅰ , Ⅱ AND X IN ARTICULAR CARTILAGE FROM MINI-PIGS

Objective According to the distribution of low selenium areas, low nutrition state of the residents and the affecting cartilage growth and articular cartilage of Kashin-Beck Disease(KBD),the chondrocyte differentia- tion and differential expression of collagen types Ⅰ , Ⅱ and Ⅹ in articular cartilage from Chinese mini-pigs treated with low selenium were investigated in order to gain insight into the effects of these conditions on chondrocyte differ- entiation in KBD cartilage. Mothods Eleven male juvenile mini-pigs, aged from 4 weeks to 6 weeks after birth, were divided into 3 groups. The Se content in the diet of the “low Se” group was 0. 035mg/kg diet, and 0. 175 mg/kg diet in the control. For Se-supplemented group 0. 390mg /kg diet was added. The content of Se in blood was assayed at the beginning and at the end of each experiment. Samples of articular cartilage were taken from the right femur condylus, and collagen types Ⅰ , Ⅱ and Ⅹ in articular cartilage were analyzed by immunohistochemistry and in situ hybridization. Results ①All cartilage samples from juvenile mini-pigs fed with low selenium diet revealed a re- duction in type Ⅹ collagen mRNA expression in the hypertrophic chondrocytes as shown by in situ hybridization, and reduced type Ⅹ collagen deposition in the lower hypertrophic zone as shown by immunohistochemistry. ②Addition of selenium to the diet restored the type Ⅹ collagen to normal level. ③Type Ⅱ collagen was evenly distributed over the entire articular cartilage in all experimental and control groups. Type Ⅱ collagen mRNA signals were most prominent in the upper articular layer as well as in the hypertrophic zone in all groups. Type Ⅱ collagen expression was restrict- ed to the zone of endochondral ossification in all experimental groups and the control. Conclusion Low selenium has an down-regulatory role on the synthesis and deposition of collagen type Ⅹ in hypertrophic chondrocytes in articular cartilage of mini-pigs. Supplement of the low Se diet with additional Se restored the signals of collagen type Ⅹ to nor- mal levels. These findings indicate that selenium deficiency may disturb chondrocyte differentiation to hypertrophic cells in the growth plate,and worthy to be investigated further.     

螺内酯对实验大鼠肝组织TGFβ1、PDGF-BB及α-SMA表达的影响

目的　探讨螺内酯预防肝纤维化的作用机制。方法　SD大鼠 90只 ,随机分为 3组。正常对照组 (8只 ) :正常饮食 ,皮下注射花生油 ;模型组 (42只 ) :复合因素制成肝纤维化模型 ;螺内酯预防组 (40只 ) :造模方法同模型组 ,螺内酯 10 0mg·kg- 1·d- 1灌胃。分别于第 2周、4周、6周、8周末随机处死 8只大鼠 ,取肝组织用免疫组化法检测各组肝组织内转化生长因子 β1(TGFβ1)、血小板衍生生长因子 (PDGF BB)及α 平滑肌动蛋白 (α SMA)含量。结果　螺内酯预防组TGFβ1、PDGF BB及α SMA在肝组织中的表达均较模型组明显减少 (P <0 .0 5或P <0 .0 1)。 结论　螺内酯可通过降低TGFβ1、PDGF BB活性及抑制肝星状细胞的活化对肝纤维化的形成起预防作用     

THE EFFECT OF LIGUSTRAZINE ON NEUROGENESIS IN CORTEX AFTER FOCAL CEREBRAL ISCHEMIA IN RATS

Objective To explore the effect of Ligustrazine on neurogenesis in cortex after focal cerebral ischemia in rats. Methods Focal cerebral ischemia was induced by left middle cerebral artery occlusion with a suture. Two hours later, injection of Ligustrazine （80 mg/kg, 1 time/d） was performed peritoneally. Four hours after the ischemia, 5-bromodeoxyuridine （BrdU） （50 mg/kg, 1 time/d） was injected peritoneally. At 7 d, 14 d and 21 d after ischemia, BrdU positive cells in the cortex were observed by cal staining. Results In ischemic model group, at 7 day, sparsely-distributed BrdU positive cells were observed in the Ⅱ-- Ⅵ layers of the ipsilateral cortex, with a bandlike distribution in ischemic penumbra. With the prolongation of ischemia, the number of BrdU positive cells increased. In Ligustrazine group, BrdU positive cells were also observed in theⅡ-- Ⅵ layers of the cortex, with an intense distribution in ischemic penumbra. The numbers of BrdU positive cells at 7 d, 14 d and 21 d were more than those in ischemic model group respectively. Conclusion Ligustrazine increases the proliferated cells in cortex after focal cerebral ischemia in rats. The results suggest that it may be useful for promoting self-repair after ischemia.     

西洋参茎叶皂甙对家兔窦房结电活动和豚鼠心肌收缩性的影响

西洋参茎叶皂甙（PanaxQuinquefoliumSaponin．PQS）200mg·L-1和800mg·L－1减慢离体家兔窦房结优势起搏细胞4相自动去极化速率，动作电位0相自动除极速率，降低窦房结动作电位幅度。PQS200mg·L－1抑制离体豚鼠心房肌静息后增强现象。结果提示，PQS具有阻断心肌细胞Ca2+内流作用。     

维甲酸致颌骨骨质疏松大鼠骨代谢变化及“双骨胶囊”治疗效果

目的　观察维甲酸致颌骨骨质疏松大鼠骨代谢变化和中药“双骨胶囊”的治疗效果。方法　将 6 0只 3月龄SD雌性大鼠随机分为二组 :正常组、模型组。模型组大鼠是以 85mg·kg-1·d-1维甲酸灌胃 15d复制模型 ,模型复制成功后进入治疗期。将模型组大鼠随机分为三组 :无措施组、双骨胶囊组和雌激素组。治疗 30d、6 0d后 ,取大鼠血、尿、下颌骨样本 ,观察治疗情况。结果　“双骨胶囊”治疗后 ,维甲酸所致颌骨骨质疏松大鼠的下颌骨骨小梁增宽 ,骨小梁之间间隔减少 ,骨髓腔缩小。骨小梁平均宽度增加 ,骨小梁平均间隔宽度减少。血清雌二醇水平显著升高 ,破骨细胞分泌的抗酒石酸酸性磷酸酶活性降低 ,血清骨钙素含量升高 ,尿钙增加。结论　治疗骨质疏松的药物“双骨胶囊”不仅对全身骨起作用 ,对治疗颌骨骨丢失也有一定的效果     

CHONDROCYTE APOPTOSIS IN ARTICULAR CARTILAGE WITH KASHIN-BECK DISEASE

Kashin BeckDisease(KBD)isachronic,en demicosteoarthritisaffectingover0.81millionspa tientsand101millionsofpeopleatriskinChina[1]. Thebasicpathologicalfeaturesofthediseaseis chondrocytesdegenerationandnecrosisinthedeep zoneofarticularcartilageandgrowthpl…     

GROWTH DIFFERENTIATION FACTOR-5 STIMULATES THE GROWTH AND ANABOLIC METABOLISM OF ARTICULAR CHONDROCYTES

Growthdifferentiationfactor5(GDF5),also knownascartilage derivedmorphogeneticprotein1(CDMP1),isamemberofthebonemorphogenet icprotein(BMP)familywhichbelongstothe transforminggrowthfactorβ(TGFβ)superfami ly[1].GDF5isarelativelynewmemberofthe BMPfamily.LikeotherBMPs,implantationofre combinantGDF5caninduceectopiccartilagefor mationinmusculartissues.Thephysiologicalrole ofGDF5hasbeenreportedincludingregulationof myogenesis,regulationofchondrogenesis,bone morphogenesis,andneurondifferen…