THE EXPRESSION OF C－erbB－1 AND C－erbB－2ONCOGENES IN BASAL CELL CARCINOMA ANDSQUAMOUS CELL CARCINOMA OF SKIN

ＴＨＥＥＸＰＲＥＳＳＩＯＮＯＦＣ－ｅｒｂＢ－１ＡＮＤＣ－ｅｒｂＢ－２ＯＮＣＯＧＥＮＥＳＩＮＢＡＳＡＬＣＥＬＬＣＡＲＣＩＮＯＭＡＡＮＤＳＱＵＡＭＯＵＳＣＥＬＬＣＡＲＣＩＮＯＭＡＯＦＳＫＩＮＬｉｕＢａｏｊｕｎ；（刘宝军），ＺｈａｎｇＨａｉｔａｏ；（张海涛...     

INCREASED EXPRESSION OF PDGF AND C－MYC GENES IN LUNGS AND PULMONARY ARTERIES OF PULMONARY HYPERTENSIVE RATS INDUCED BY HYPOXI

ＩＮＣＲＥＡＳＥＤＥＸＰＲＥＳＳＩＯＮＯＦＰＤＧＦＡＮＤＣ－ＭＹＣＧＥＮＥＳＩＮＬＵＮＧＳＡＮＤＰＵＬＭＯＮＡＲＹＡＲＴＥＲＩＥＳＯＦＰＵＬＭＯＮＡＲＹＨＹＰＥＲＴＥＮＳＩＶＥＲＡＴＳＩＮＤＵＣＥＤＢＹＨＹＰＯＸＩＡ￥ＣａｉＹｉｎｇｎｉａｎ；（蔡英年...     

CHANGES OF IMMUNE FUNCTIONS AFTER RADIATION，BURNS AND COMBINED RADIATION－BURN INJURY IN RATS

ＣＨＡＮＧＥＳＯＦＩＭＭＵＮＥＦＵＮＣＴＩＯＮＳＡＦＴＥＲＲＡＤＩＡＴＩＯ，ＢＵＲＮＳＡＮＤＣＯＭＢＩＮＥＤＲＡＤＩＡＴＩＯＮ－ＢＵＲＮＩＮＪＵＲＹＩＮ　ＲＡＴＳＹａｎＹｏｎｇｔａｎｇ（阎永堂）；ＲａｎＸｉｎｚｅ（冉新泽）ａｎｄＷｅｉＳｈｕｑｉｎｇ（...     

EFFECT OF THE EXCITATION OF ADRENOCEPTORS ON THE PACEMAKER CURRENT I_f OF SHEEP CARDIAC PURKINJE FIBRES IN “ISCHEMIA” SOLUTIO

ＥＦＦＥＣＴＯＦＴＨＥＥＸＣＩＴＡＴＩＯＮＯＦＡＤＲＥＮＯＣＥＰＴＯＲＳＯＮＴＨＥＰＡＣＥＭＡＫＥＲＣＵＲＲＥＮＴＩ_ｆＯＦＳＨＥＥＰＣＡＲＤＩＡＣＰＵＲＫＩＮＪＥＦＩＢＲＥＳＩＮ“ＩＳＣＨＥＭＩＡ”ＳＯＬＵＴＩＯＮＸｕＹｏｕｑｉｕ（徐有秋），Ｚｈａ?..     

EFFECT OF EXCITATORY AMINO ACIDS．Ca~（2＋） ON DELAYED NEURONAL DEATH IN HIPPOCAMPUS FOLLOWING TRANSIENT FOREBRAINISCHEMIA IN GE

ＥＦＦＥＣＴＯＦＥＸＣＩＴＡＴＯＲＹＡＭＩＮＯＡＣＩＤＳ．Ｃａ~（２＋）ＯＮＤＥＬＡＹＥＤＮＥＵＲＯＮＡＬＤＥＡＴＨＩＮＨＩＰＰＯＣＡＭＰＵＳＦＯＬＬＯＷＩＮＧＴＲＡＮＳＩＥＮＴＦＯＲＥＢＲＡＩＮＩＳＣＨＥＭＩＡＩＮＧＥＲＢＩＬＳ￥ＸｕＣｈａｎｇｑｉ?..     

CHANGES OF ENDOTHELIN-1 GENE EXPRESSION IN RAT BRAINS DURING ISCHEMIA AND ISCHEMIC REPERFUSION

ＣＨＡＮＧＥＳＯＦＥＮＤＯＴＨＥＬＩＮ－１ＧＥＮＥＥＸＰＲＥＳＳＩＯＮＩＮＲＡＴＢＲＡＩＮＳＤＵＲＩＮＧＩＳＣＨＥＭＩＡＡＮＤＩＳＣＨＥＭＩＣＲＥＰＥＲＦＵＳＩＯＮＷｕＷｅｉｐｉｎｇ（吴卫平）；ＫｕａｎｇＰｅｉｇｅｎ（匡培根）ａｎｄＬｉＺｈｅｎｚｈｏ...     

EFFECTS OF MTX AND BN_52021 ON PAF－INDUCED CHEMOTAXIS OF PMNs AND I

ＥＦＦＥＣＴＳＯＦＭＴＸＡＮＤＢＮ５２０２１ＯＮＰＡＦ－ＩＮＤＵＣＥＤＣＨＥＭＯＴＡＸＩＳＯＦＰＭＮｓＡＮＤＩＮＴＲＡＥＰＩＤＥＲＭＡＬＡＣＣＵＭＵＬＡＴＩＯＮＯＦＩＮＦＬＡＭＭＡＴＯＲＹＣＥＬＬＳＩＮＧＵＩＮＥＡＰＩＧＳＬｉｕＢａｏｊｕｎ刘宝军，Ｚ...     

ANTITUMOR ACTIVITY OF IMMUNOCONJUGATES COMPOSED OF BOANMYCIN AND MONOCLONAL ANTIBODY

ＡＮＴＩＴＵＭＯＲＡＣＴＩＶＩＴＹＯＦＩＭＭＵＮＯＣＯＮＪＵＧＡＴＥＳＣＯＭＰＯＳＥＤＯＦＢＯＡＮＭＹＣＩＮＡＮＤＭＯＮＯＣＬＯＮＡＬＡＮＴＩＢＯＤＹ￥ＺｈｅｎＹｏｎｇｓｕ；（甄永苏）；ＰｅｎｇＺｅ（彭泽）；ＤｅｎｇＹｏｎｇｃｈｕａｎ；（邓甬川）Ｘｕ...     

EXPRESSION OF TGF－β_1，PDGF AND IGF－1 mRNA IN LUNG OF BLEOMYCIN－A_5－INDUCED PULMONARY FIBROSIS IN RATS

ＥＸＰＲＥＳＳＩＯＮＯＦＴＧＦ－β１，ＰＤＧＦＡＮＤＩＧＦ－１ｍＲＮＡＩＮＬＵＮＧＯＦＢＬＥＯＭＹＣＩＮ－Ａ５－ＩＮＤＵＣＥＤＰＵＬＭＯＮＡＲＹＦＩＢＲＯＳＩＳＩＮＲＡＴＳＬｉＨａｉｃｈａｏ李海潮，ＨｅＢｉｎｇ何冰，ＱｕｅＣｈｅｎｇｌｉ阙呈立ａｎｄＷ...     

A STUDY ON DETECTION OF SERUM FASTING TOTAL BILE ACID AND CHOLOYGLYCIN IN NEONATE FOR CHOLESTASIS

ＡＳＴＵＤＹＯＮＤＥＴＥＣＴＩＯＮＯＦＳＥＲＵＭＦＡＳＴＩＮＧＴＯＴＡＬＢＩＬＥＡＣＩＤＡＮＤＣＨＯＬＯＹＧＬＹＣＩＮＩＮＮＥＯＮＡＴＥＦＯＲＣＨＯＬＥＳＴＡＳＩＳＧｕｏＷｅｎ（郭文）；ＷｕＭｉｎｇｃｈａｎｇ（吴明昌）；ＰｅｉＸｕｅｙｉ（裴学义）；Ｇ...     

Evidence of apoptotic smooth muscle cells in proliferative intima of injured arteries

Objective To investigate the occurrence and extent of apoptosis in the course of restenosis. Methods The experimental models of vessel narrowness and intima thickness were established in minipigs’ iliac arteries by balloon injury and specimens were retrieved on the 1st, 3rd, 6th,12th and 30th days for dynamic observation. Apoptotic smooth muscle cells (SMCs) were detected by terminal deoxynucleotidyl transferase- mediated dUTP nick- end labeling (TUNEL). Results Apoptotic SMCs occurred only in the thickened intima 12 days after injury accompanied with the proliferative SMCs, the percentage of apoptosis was 1. 94%±0. 42% on the 12th day and 1. 36%±0. 31% on the 30th day respectively. The low frequency of apoptosis compared with the proliferative SMCs was a feature in the restenotic pathology. Conclusions Apoptosis participates in the pathogenetic process of intimal thickening and its level was low compared with proliferation. The findings suggest that attempts to modulate apoptosis after vessel injury constitute a theoretical approach to the prevention of restenosis.     

INHIBITORY EFFECT OF FLUVASTATIN ON AORTIC INTIMAL THICKENING IN NORMOCHOLESTEROLEMIC RABBITS

Objective, The anti-atherosclerotic effect of fluvastatin at doses insufficient to lower serum cholesterol on the catheter-induced intimal thickening and possible mechanism were investigated in abdominal aorta of rabbits. Methods. Fifty-six rabbits were randomly divided into eight groups( n = 7, each). Fluvastatin was given mixed with food at daily dose of 8mg/kg starting 5 days before catheterization. Light microscope, immanohistochemistry, transmis-sion electron microscope and RT-PCR assay were applied to assess vascular smooth muscle cell (VSMC) proliferation and apoptosis, as well as oncogene expression in vascular wall. Results. At day 10 and day 15 after catheter induced denudation intima/media( I/M) thickness ratio was obviously higher, and also the percentage of PCNA-positive cells and TUNEL-positive cells in media was significantly higher compared with controls. The intimal hyperplasia was mostly composed of α-SM-actin-pesitive cells. In rabbits given flu-vastatin I/M ratio and the percentage of these positive cells significantly decreased compared with those without fluvas-tatin.The overexpression of proto-oncogene H-ras mRNA and decreased expression of anti-oncogene p53 mRNA were found after vascular injury, whereas fluvastatin significantly reduced H-ras mRNA and increased p53 mRNA expres-sion. Conclusion. Proliferation of VSMC in the media and the migration to the intima can be inhibited, and apoptosis of VSMC be induced by short-term use of fluvastatin after balloon catheter denudation, independent of serum lipid change. The underlying mechanism is presumably associated With the influence of fluvastatin on oncogene expression in the injured vascular Wall.     

The Role of NF-kB and I-kB in Intimal Proliferation Following Balloon Catheter-induced Injury in the Rat Carotid Artery

The aim of our study was to gain insight into the molecular and cellular mechanisms of post-angioplasty restenosis using balloon catheter-induced injury model in the rat carotid artery. SD rats were subjected balloon catheterization at one side carotid artery as study group and another side as control group. Six rats were killed on the 6 h, and 3rd, 7th, 14th, 28th day after balloon-induced injury respectively. The intimal thickness and the expression of NF-κB and I-κB were detected by HE-staining, gel electrophoretic mobility shift assay （EMSA） and Western-blot methods. The results showed that： （1） The thickening of intima was observed on the 3rd day after balloon-induced injury, and it became more significant on the 7th, 14th and 28th day. The area ratio of intima/media was increased significantly （P〈0.05）; （2） The expression of NF-κB was not detectable in the control group, however, in study group, the expression of NF-κB was detected on the 6th h after balloon-induced injury, reached the peak on the 14th day, and on 28th day, strong expression of NF-κB was observed; （3） The expression of I-κB protein was reduced after balloon-induced injury, and there were significant differences between the study group and the control group （P〈0.05）. It was concluded that the alteration of NF-κB/I-κB system might play an important role in aberrant proliferation within the intima and vascular remodeling following vascular injury. To block NF-κB activation and its role in arterial restenosis initiation may potentially provide a novel therapeutic tool for the treatment and prevention of arterial restenosis.     

EXPRESSION AND ROLE OF PLASMINOGEN SYSTEM IN PROCESS OF RESTENOSIS

Objective To study the expression and role of plasminogen system in the process of restenosis. Methods We established a double-injury model of atherosclerotic restenosis in rabbit iliac artery mimicking human arterial restenosis. The time course of tissue plaminogen activator （ tPA ）, urokinase plasminogen activator （ uPA ）, urokinase plasminogen activator receptor （uPAR） and plasminogen activator inhibitor-1 （ PAI-1 ） was investigated by immunohistochemistry. The mRNA expression of uPA and uPAR were detected after vascular procedures by in situ hybridization. Results In uninjured arteries, the weak expression of tPA and PAI-1 was detected in intimal and endothelial cells. The expression of tPA, uPA, uPAR and PAI-1 was significantly induced after double-injury, but after double-injury 14d, the expression of tPA restore to preinjury levels. The expression of uPA and uPAR in intimal was higher than that of media and maintain high levels in intimal within 42d and 56d. Conclusion Whereas t-PA is primarily involved in clot dissolution and play a limited role in the process of restenosis, in plasminogen system, uPA and uPAR play a prominent role in the process of restenosis.     

增殖期再狭窄血管平滑肌细胞中表皮生长因子受体的表达

目的：探讨动脉成形术后血管平滑肌细胞（ＳＭＣ）表皮生长因子受体（ＥＧＦＲ）在再狭窄发生机理中的作用。方法：取正常家兔髂动脉、高脂血症兔髂动脉成形术后２周非狭窄段和狭窄段ＳＭＣ，分别用Ｎｏｒｔｈｅｒｎ杂交和免疫组化法检测３种静止期ＳＭＣ及增殖期再狭窄ＳＭＣ中ＥＧＦＲ的表达。结果：３种静止期ＳＭＣ均未见ＥＧＦＲｍＲＮＡ表达，而再狭窄ＳＭＣ受血清刺激后４ｈ即有ＥＧＦＲｍＲＮＡ表达，至指数生长期表达更明显。免疫组化显示ＥＧＦＲ蛋白质仅在指数生长期ＳＭＣ中显现阳性反应，其阳性颗粒定位于细胞膜。结论：ＥＧＦＲ表达增加与再狭窄过程中ＳＭＣ增殖有关。     

腺病毒载体转染大鼠颈动脉的实验研究

目的观察腺病毒载体转染大鼠颈动脉的有效性和外源性基因表达的时间过程。方法用ＡｄＶ５－ＣＭＶ质粒（对照组）或Ａｄｖ５－ＣＭＶ／ＬａｃＺ质粒（治疗组）转染大鼠颈动脉３０分钟。术后２、７、１４、２８、６０及９０天取被转染的颈动脉,行β－半乳糖苷酶活性测定和组织化学染色。结果对照组所有颈动脉均无β－半乳糖苷酶活性,治疗组术后２天颈动脉即有β－半乳糖苷酶的表达,７～１４天为表达高峰期,２８天后表达量明显减少,但可持续表达３个月之久。治疗组术后２、７、１４、２８、６０及９０天每条颈动脉均可见蓝染,其中术后７及１４天每条颈动脉横切面的全周均有蓝染,血管壁内层、中层的大部分细胞被染成蓝色。对照组所有动脉均未见蓝染。结论腺病毒载体能高效转染大鼠在体颈动脉。转染后,外源性基因的高水平表达只能维持１个月左右。     

生长因子-1诱骗寡核苷酸对大鼠颈总动脉球囊损伤后血小板源性生长因子-BB表达的影响

目的探讨针对早期生长反应因子-1（Egr-1）的诱骗性寡脱氧核苷酸（decoy ODN）对大鼠动脉损伤后内膜增生的影响和可能的机制。方法制备大鼠颈动脉球囊损伤模型,将96只Wistar大鼠随机分为假手术组、单纯损伤组、杂码寡脱氧核苷酸（SCR）组和治疗组,每组24只。术后3、7、14、21 d处死动物,每组6只。应用HE染色、Real time RT-PCR和Western blot方法观察大鼠颈动脉球囊损伤后内膜增生情况、Egr-1和血小板源性生长因子-BB（PDGF-BB）的表达及Egr-1 decoy ODN对它们的影响。结果①内皮损伤后3 d内膜增厚不明显,7 d内膜开始增厚,14、21 d时内膜明显增厚。②Egr-1 mRNA和蛋白水平于术后3 d开始升高,21 d时达到顶峰,而PDGF-BB的mRNA和蛋白水平均于3 d开始升高,14 d时达到顶峰。③转染Egr-1 decoy ODN治疗后,在各个时间点内膜增厚程度减轻,与对照组比较,Egr-1和PDGF-BB表达明显减少,差异有高度统计学意义（P〈0.01）。结论 Egr-1 decoy ODN可能是通过特异性抑制Egr-1的表达,进而抑制PDGF-BB的表达,达到减轻新生内膜厚度、从而减轻血管损伤后内膜增生的目的。     

血管内放射对猪受损髂动脉平滑肌细胞增殖与凋亡的影响

目的 :观察血管内放射照射对猪髂动脉球囊损伤后血管新生内膜平滑肌细胞(SMC)增殖与凋亡的影响。方法 :2 7头小型猪分为 3组 ,所有猪行髂动脉球囊过大扩张 ,通过后装装置将 1 0Gy和 2 0Gy的192 Ir放射源分别置于 9只猪受损髂动脉部位 ,其他 9只猪的受损髂动脉作为对照。每组的 9头猪分别术后 3天、1 0天和 2 8天分 3次处死。用增殖细胞核抗原(PCNA)和三磷酸脱氧尿嘧啶缺口末端标记法 (TUNEL)法检测内膜SMC增殖和凋亡情况。结果 :代表血管内膜增殖的PCNA指数在 1 0天和 2 8天宰杀的猪中 ,放射治疗组明显低于对照组。术后 1 0天内膜SMC凋亡在对照组和 1 0Gy、2 0Gy组的值分别为 :(1 85± 0 49) %比 (2 2 7± 0 49) %(P >0 0 5)和 (1 85± 0 49) %比 (2 53± 0 45) %(P <0 0 5) ;术后 2 8天上述值分别为(1 61± 0 3 5) %比 (3 1 1± 0 51 ) %(P <0 0 5)和 (1 61± 0 3 5) %比 (7 0 5± 1 82 ) %(P <0 0 5) ;2 8天时 2 0Gy组的内膜SMC凋亡明显高于 1 0Gy组 (7 0 5± 1 82 ) %比 (3 1 1± 0 51 ) %(P <0 0 5)。相同的放射剂量时 ,2 8天宰杀猪的髂动脉SMC凋亡高于 1 0天宰杀猪的量。结论 :血管内γ射线照射能抑制小型猪球囊损伤髂动脉内膜SMC增殖和刺激SMC凋     

Hypoxia-inducible factor-1 alpha regulates the role of vascular endothelial growth factor on pulmonary arteries of rats with hypoxia-induced pulmonary hypertension

Background Hypoxia-inducible factor-1α (HIF-1α) is one of the pivotal mediators in the response of lungs to decreased oxygen availability, and increasingly has been implicated in the pathogenesis of pulmonary hypertension. Vascular endothelial growth factor (VEGF), a downstream target gene of HIF-1α, plays an important role in the pathogenesis of hypoxic pulmonary hypertension and hypoxic pulmonary artery remodelling. In this study, we investigated the dynamic expression of HIF-1α and VEGF in pulmonary artery of rats with hypoxia-induced pulmonary hypertension. Methods Forty male Wistar rats were exposed to hypoxia for 0, 3, 7, 14 or 21 days. Mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle hypertrophy index (RVHI) were estimated. Lungs were inflated and fixed for in situ hybridisation and immunohistochemistry. Results mPAP values were significantly higher than the control values after 7days of hypoxia ［(18.4±0.4) mmHg, P&lt;0.05］. RVHI developed significantly after 14 days of hypoxia. Expression of HIF-1α protein increased in pulmonary arterial tunica intima of all hypoxic rats. In pulmonary arterial tunica media, HIF-1α protein was markedly increased by day 3 (0.20±0.02, P&lt;0.05), reached the peak by day 7, then declined after day 14 of hypoxia. HIF-1α mRNA increased significantly after day 14 of hypoxia （0.20±0.02, P&lt;0.05）. VEGF protein began to increase markedly after day 7 of hypoxia, reaching its peak around day 14 of hypoxia (0.15±0.02, P&lt;0.05). VEGF mRNA began to increase after day 7 of hypoxia, then remained more or less stable from day 7 onwards. VEGF mRNA is located mainly in tunica intima and tunica media, whereas VEGF protein is located predominantly in tunica intima. Linear analysis showed that HIF-1α mRNA, VEGF and mPAP were correlated with hypoxic pulmonary artery remodelling. HIF-1α mRNA was positively correlated with VEGF mRNA and protein (P&lt;0.01). Conclusion HIF-1α and VEGF are both involved in the pathogenesis of hypoxia-induced pulmonary hypertension in rats.     

二苯乙烯苷对大鼠颈动脉球囊损伤后内膜增生的作用

目的 观察二苯乙烯苷对大鼠颈动脉球囊损伤后内膜增生和细胞外信号调节激酶（ERK）表达的影响.方法 将SD大鼠随机分为假手术组、手术组和二苯乙烯苷组（TSG组）.手术组及TSG组均用球囊导管扩张法损伤左侧颈总动脉,TSG组给予二苯乙烯苷灌胃治疗.术后第7天、14天和21天,取损伤血管行苏木精-伊红染色、免疫组化染色及光镜观察,利用计算机图像分析仪分别测量血管内膜和中膜横断面的面积,计算内膜/中膜面积比（I/M）,并用Western Blot检测血管组织中细胞外信号调节激酶（pERK1/2）蛋白表达.结果 与假手术组比较,球囊导管扩张法损伤的左侧颈总动脉内膜/中膜面积比显著增加,受损血管的ERK1/2蛋白的磷酸化加强,二苯乙烯苷能够减少内膜/中膜面积比,抑制pERK1/2的蛋白表达（P〈0.05）.结论二苯乙烯苷抑制内膜增生、延缓损伤血管狭窄的作用可能与减少血管ERK表达有关.