RNA干扰技术阻抑热休克蛋白对瘢痕疙瘩生成的影响

目的利用RNA干扰（RNAi）技术，通过热休克蛋白47重组质粒（HSP47siRNA）和脂质体的混合液，对瘢痕疙瘩裸鼠动物模型的体内干预后，分析HSP47基因在瘢痕疙瘩生成中的作用。方法构建裸鼠瘢痕疙瘩动物模型，于第16天腹腔麻醉后在实验组瘢痕疙瘩内注射质粒、脂质体混合液0．25ml，对照组裸鼠腹腔注射磷酸缓冲液（PBS）0．25ml，原笼饲养，7d回收标本，分别做mRNA水平检测、胶原蛋白水平检测以及免疫组织化学检测。结果实验组HSP47mRNA表达明显降低，且实验组总胶原含量，I型胶原蛋白mRNA表达与对照组比较也明显降低，差异均有统计学意义（P〈0．05）。结论利用RNAi技术，通过过HSP47siRNA表达载体特异性沉默瘢痕疙瘩中HSP47基因表达后，瘢痕疙瘩中胶原蛋白的合成和分泌均能得到明显抑制，表明HSP47基因具有促进瘢痕疙瘩生成作用，为抑制瘢痕疙瘩提供新的靶点。     

Ergothioneine modulates proinflammatory cytokines and heat shock protein 70 in mesenteric ischemia and reperfusion injury

BACKGROUND AND AIM: Ergothioneine (EGT) is a natural compound that is synthesized by soil bacteria in fungal substrates and exhibits antioxidant functions in many cell models. The purpose of this study was to investigate the effect of EGT on mesenteric ischemia and reperfusion injury. MATERIALS AND METHODS: Rats were supplemented with or without l-ergothioneine (10 mg/kg/d) for 15 days prior to intestinal ischemia. Animals were subjected to ischemia induced by clamping the superior mesenteric artery for 60 min followed by reperfusion. Serum tumor necrosis factor (TNF)-alpha and interleukin-1beta (IL-1beta) levels, tissue malondialdehide (MDA), myleoperoxidase (MPO), and heat shock protein (HSP) 70 levels, as well as histological findings, were evaluated after 1, 2, and 4 h of reperfusion. RESULTS: Serum TNF-alpha and IL-1beta levels, and tissue MDA and MPO activities at 1, 2 and 4 h after reperfusion in the EGT group, were significantly lower than the control group (P < 0.05). Tissue HSP-70 levels of the study group were significantly greater than the control group at any time point of reperfusion. No significant differences in tissue damage including morphological changes ranging from villous denudation to focal necrosis, ulceration, hemorrhage, and architectural disintegration at 1 and 2 h after reperfusion exist between the two groups; however, after 4 h of reperfusion, the tissue damage based on histopathologic scores by Chiu was considerably lower in the study group (P < 0.05). After 4 h of reperfusion, focal epithelial lifting and occasional areas of denuded villi could be seen in the samples of the treated animals, thus preserving villous height and mucosal architecture. CONCLUSION: EGT attenuates mesenteric ischemia reperfusion injury in rat intestine by increasing tissue HSP-70 and decreasing TNF-alpha, IL-1beta, MDA, and MPO levels. EGT also improves morphological alterations, which occurred after IR injury after prolonged periods of reperfusion.     

热休克蛋白90对大鼠缺氧心肌细胞丝氨酸苏氨酸蛋白激酶表达的影响

目的探讨内源性热休克蛋白90（HSP90）在缺氧心肌细胞丝氨酸苏氨酸蛋白激酶（AKT）相关信号通路中的作用。方法建立新生Wistar大鼠心肌细胞缺氧模型，将细胞分为正常组、缺氧组、加入HSP90特异性阻断剂格尔德霉素后再缺氧组（格尔德霉素＋缺氧组）。于缺氧后1、3、6、12、24、48h用噻唑蓝法检测心肌细胞的活力；缺氧24h，原位缺口末端标记法检测心肌细胞凋亡指数（AI）；缺氧1、3、6、12、24h，蛋白质印迹法检测大鼠心肌细胞中内源性HSP90及AKT表达水平。结果（1）缺氧24、48h，缺氧组、格尔德霉素＋缺氧组细胞活力均较正常组明显下降（P〈0．05）；格尔德霉素＋缺氧组细胞活力缺氧12h即开始明显下降，缺氧48h时明显低于缺氧组（P〈0．05）。（2）缺氧24h，缺氧组细胞AI为（10．7±1．2）％，明显高于正常组[（1．9±0．3）％．P〈0．05]；格尔德霉素＋缺氧组细胞AI为（26、3±5．3）％，明显高于缺氧组（P〈0．01）。（3）缺氧12h，缺氧组心肌细胞内源性HSP90及AKT表达水平高于正常组与格尔德霉素＋缺氧组；缺氧24h，缺氧组有所下降．格尔德霉素＋缺氧组则下降更明显。结论内源性HSP90对维持心肌细胞的活力有重要作用．缺氧心肌细胞AKT表达水平可受内源性HSP90表达水平的影响。     

Achilles tendon healing: long-term biomechanical effects of postoperative mobilization and immobilization in a new mouse model.

The aim of the study was to investigate the long-term effects of postoperative immobilization as opposed to mobilization on the biomechanical attributes of healing Achilles tendons in a new experimental mouse model. In 114 Balb-C-mice the left Achilles tendon was transected and sutured by the Kirchmayr-Kessler technique. The tendons healed either under postoperative immobilization effected by fixing the upper ankle joint in equinus position or under mobilization through a limited range of movement. The contralateral Achilles tendons served as internal control. All tendons were tested biomechanically at short intervals up to the 112th postoperative day in terms of load to failure [N], tendon deflection [mm] and tendon stiffness [N/mm], and were evaluated histologically after 8 and 112 days. Postoperative mobilization resulted in a continuous and significantly more rapid restoration of load to failure in comparison to the immobilization group. Tendon deflection was decreased by postoperative mobilization, whereas under immobilization it paradoxically increased still further in the later course. After 112 days the tendons of the mobilization group had regained their original tendon stiffness, whereas the tendons after immobilization reached only about half the values seen in the control tendons. Histologically, postoperative mobilization led to increased immigration of inflammatory cells in the early phase. In the late phase, as compared to immobilization, tendon structure was more mature, with fibre bundles arranged in parallel and interposed tendocytes. Tensile loading of the healing tendon by postoperative mobilization leads to fundamental changes in the biological process of tendon healing resulting in accelerated restoration of load to failure and reduced tendon deflection.     

Effect of heat shock protein 47 on collagen synthesis of keloid in vivo

Keloid is regarded as a fibroproliferative disorder with excessive accumulation of extracellular matrix. However, the molecular mechanism of keloid formation is not well understood and no treatment modality is consistently effective. Heat shock protein 47 (HSP47) is known as a collagen-specific molecular chaperone which plays a critical role in collagen biosynthesis. Results of our previous in vitro experiments demonstrated that HSP47 might be an important reason for excessive collagen accumulation in regard to keloid formation. Our objective is to investigate whether HSP47 has an influence on collagen metabolism in animal keloid models. The constructed plasmids, carrying HSP47-small hairpin RNA (shRNA), were transfected into animal keloid models, in comparison with the control groups. After transfection, the mRNA and protein expression of HSP47 and collage type I were detected by quantitative real-time PCR and Western blot. Both the mRNA and protein levels of HSP47 in animal keloid models were decreased dramatically after transfection of the HSP47- shRNA plasmid, in comparison with the control group. Following the down-regulation of HSP47, we found that the volume of animal keloid models and the major collagen expression were reduced correspondingly. Combining the results of our previous in vitro experiment results, we suggest that overexpression of HSP47 in keloid fibroblast cells could induce excessive collagen accumulation by enhancing collagen synthesis, which not only presents a possible mechanism of keloid formation, but also offers a therapeutic potential of RNA interference to HSP47 for the treatment of keloids and other fibroproliferative disorders.     

糖皮质激素受体和热休克蛋白70在大鼠重症急性胰腺炎中的表达

目的 探讨糖皮质激素受体(glucocorticoid receptor,GR)和热休克蛋白70(heat shock protein70,HSP70)在大鼠重症急性胰腺炎(severe acute pancreatitis,SAP)中的变化及意义.方法 48只健康雄性SD大鼠,随机分成SAP组、阻断GR组和正常对照组,每组16只.采用逆行胆胰管注射牛磺胆酸钠造成SAP模型,制模前15 h肌注10%Ru486(米非司酮)油剂(按5 mg/kg体质量肌肉注射)阻断GR50%.12 h后分别活杀观察胰腺、肝、肾、肺、小肠的病理改变并采用免疫印迹法测定各组织的GR,HSP70含量.结果 SAP组和阻断GR组大鼠各组织的GR水平明显低于正常对照组(P＜0.01),HSP70明显高于正常对照组(P＜0.01).阻断GR组各组织的GR和HSP70含量明显低于SAP组(P＜0.01).12 h时模型组大鼠的胰腺、肝、肾、肺、小肠已有明显的病理改变,阻断GR模型组的病理改变较SAP组明显加重.结论 在重症急性胰腺炎大鼠模型中存在GR水平的降低和HSP70水平的升高,GR不足是导致重症急性胰腺炎早期继发性肝、肾、肺、小肠损伤的重要原因,它可能通过HSP70表达下降起作用.     

低氧预适应诱导HSP70对大鼠肝癌切除术后炎症介质的调控作用

目的:探讨低氧预适应诱导热休克蛋白70(HSP70)在大鼠肝癌切除术后残肝组织调控炎症介质的作用及可能的机制。方法:制备SD大鼠种植性肝癌模型,将模型鼠随机分为假手术组(SO组)、缺血状态下肝癌切除组(IR组)和低氧预适应+缺血状态下肝癌切除组(HP组),每组20只。HP组的处理方式:术前给予10%氮氧混合气体处理90 min,Pringle法完全阻断入肝血流15 min,行肿瘤所在的肝左外叶切除。各组分别于术后1、8、12、24 h取残余肝脏标本,分别用Western blot法检测HSP70、核转录因子NF-κB p65相对表达量,ELISA法检测TNF-α、IL-1β含量,并在光镜下观察各组组织形态学改变。结果:HP组经低氧预适应后,HSP70的表达明显增加,而NF-κB p65的表达及TNF-α、IL-1β的含量均明显降低,病理损伤减轻。HSP70在SO、IR组仅有微量表达,两组间无统计学差异。结论:低氧预适应对肝癌肝切除术后缺血残肝IR损伤有保护作用,其机制可能与增加HSP70的表达,进而抑制NF-κB的活性及TNF-α、IL-1β的表达有关。     

Study of apoptosis and heat shock protein (HSP) expression in hepatocytes following radiofrequency ablation (RFA)

BACKGROUND: Radiofrequency ablation (RFA) of the liver produces necrosis of the hepatocytes. Histological examination shows a sharp demarcation between ablated and normal liver tissue. This experiment was carried out to study the cellular injury produced by RFA in area surrounding the ablated tissue and effect of reperfusion on this zone. MATERIAL AND METHODS: Five pigs underwent RFA of liver parenchyma. Four pigs were sacrificed 30 min after RFA and one pig was sacrificed 5 days later. Ablated lesions including surrounding liver parenchyma was examined for apoptosis and HSP 70 expression. RESULTS: There was a zone of transition surrounding the necrotic ablated area that showed apoptosis as well as increased HSP 70 expression. This was more prevalent in the pig that was sacrificed 5 days later. CONCLUSION: RFA produces sub lethal injury in the zone of transition causing apoptosis and increase in HSP 70 expression. Increased HSP expression enhances immunogenicity of these cells that can have therapeutic implications for the treatment of liver.     

Evaluation of warm ischemia-reperfusion injury using heat shock protein in the rat liver

We focused on heat shock protein 70 (HSP70) as a marker of viability in hepatic warm ischemia-reperfusion. Segmental hepatic warm ischemia was produced in rats for 15, 30, 60, 90, 120, or 180 min. Liver sections were evaluated at 30, 60, and 120 min of reperfusion. Expression of HSP70 and messenger RNA (mRNA), apoptosis, and apoptosis-associated genes such as Bcl-2 and Bax were studied. Expression of HSP70 and mRNA was augmented as warm ischemia was prolonged, but was markedly suppressed in livers with more than 120 min of ischemia. The highest accumulation of HSP70 was observed in the nucleus. In livers subjected to longer duration of warm ischemia, necrosis and apoptosis were evident and Bcl-2 mRNA expression and Bcl-2/Bax protein ratio were markedly diminished. Apoptosis may be related to the process of cellular injury induced by warm ischemia-reperfusion. Expression of HSP70 and the Bcl-2 family can be effective markers of viability in hepatic warm ischemia-reperfusion.     

热休克蛋白70在肝血流间断阻断再灌注后的表达及作用

目的：探讨热休克蛋白70（HSP70）在肝血流间断和持续阻断再灌注后的表达及作用。方法：将实验大鼠分为持续阻断组，间断阻断组和假处理组，用免疫金银法观察再灌注1h后肝组织中HSP70的表达，并检测肝细胞及线粒体功能。结果：HSP70面肝持续性缺血再灌注后无表达，肝细胞和线粒体功能均显著下降，间断性血流阻断组则有HSP70的合成表达，该组与假处理组的肝细胞和线粒体功能指标的差异均无显著性。结论：HSP70在间断性肝血流阻断再灌注后的早期合成，有利于保护肝细胞和线粒体功能。     

雾化吸人利多卡因对哮喘大鼠肺组织热休克蛋白70、核因子κB表达的影响

Objective To observe the effect of aerosolized lidocaine inhalation on expression of HSP70 and NF-ΚB in lung of asthma rat model. Methods Thirty two Wistar rats were randomly assigned to four groups (n=8 each): control group( group A), asthma model group(group B),dexamethasone group(group C)and lidocaine group(group D). The rats in group B were sensitized by injection of ovalbumin(OA )together with aluminum hydroxide as adjuvants, followed by aerosolized OA challenge two weeks later. The rats in group C and D were sensitized with OA as group B, but exposed to 0.02% aerosol of dexamethasone and 0.04% aerosol of lidocaine 20 ml respectively. In group A saline was used instead of OA. In 24 hours after the last challenge, the lungs were removed for microscopic examination, determination of W/D lung weight radio, the expression of HSP70 and NF-ΚB was studied immunohistochemically.Results①The W/D lung weight radio were 4.08±0.16,3.54±0.10 and 3.66±0.12 respectively in group B,C,D,more than the group A with 3.30±0.12. ② The pulmonary expression of HSP70 were 0.210±0.018,0.138±0.010 and 0.154±0.012 respectively in group B,C,D, higher than the group A with 0.049±0.015. ③The pulmonary expression of NF -KB were 0.199±0.029,0.132±0.010 and 0.150±0.017respectively in group B, C, D, higher than the group A with 0.056±0.022. ④Compared with the group B, the W/D lung weight radio and pulmonary expression of HSP70 and NF -ΚB in group C and D were significantly down -regulated. In animals with asthma the bronchial walls were significantly thicker with inflammatory cell infiltration. Dexamethasone or lidocaine aerosolized inhalation significantly attenuated the pathologic changes induced by asthma. Conclusion Aerosolized lidocaine inhalation has a protective effect on airway inflammation and histology damages resulting from aeroallergen challenge in the asthma model of Wistar rats.     

雾化吸人利多卡因对哮喘大鼠肺组织热休克蛋白70、核因子κB表达的影响

Objective To observe the effect of aerosolized lidocaine inhalation on expression of HSP70 and NF-ΚB in lung of asthma rat model. Methods Thirty two Wistar rats were randomly assigned to four groups (n=8 each): control group( group A), asthma model group(group B),dexamethasone group(group C)and lidocaine group(group D). The rats in group B were sensitized by injection of ovalbumin(OA )together with aluminum hydroxide as adjuvants, followed by aerosolized OA challenge two weeks later. The rats in group C and D were sensitized with OA as group B, but exposed to 0.02% aerosol of dexamethasone and 0.04% aerosol of lidocaine 20 ml respectively. In group A saline was used instead of OA. In 24 hours after the last challenge, the lungs were removed for microscopic examination, determination of W/D lung weight radio, the expression of HSP70 and NF-ΚB was studied immunohistochemically.Results①The W/D lung weight radio were 4.08±0.16,3.54±0.10 and 3.66±0.12 respectively in group B,C,D,more than the group A with 3.30±0.12. ② The pulmonary expression of HSP70 were 0.210±0.018,0.138±0.010 and 0.154±0.012 respectively in group B,C,D, higher than the group A with 0.049±0.015. ③The pulmonary expression of NF -KB were 0.199±0.029,0.132±0.010 and 0.150±0.017respectively in group B, C, D, higher than the group A with 0.056±0.022. ④Compared with the group B, the W/D lung weight radio and pulmonary expression of HSP70 and NF -ΚB in group C and D were significantly down -regulated. In animals with asthma the bronchial walls were significantly thicker with inflammatory cell infiltration. Dexamethasone or lidocaine aerosolized inhalation significantly attenuated the pathologic changes induced by asthma. Conclusion Aerosolized lidocaine inhalation has a protective effect on airway inflammation and histology damages resulting from aeroallergen challenge in the asthma model of Wistar rats.     

联合信号转导和转录激活因子3与热休克蛋白90鉴别良恶性嗜铬细胞瘤的探讨

目的:通过检测热休克蛋白90(HSP90)与信号转导和转录激活因子3(STAT3)在良恶性肾上腺嗜铬细胞瘤中的表达情况,探讨HSP90和STAT3在早期诊断恶性嗜铬细胞瘤中的价值。方法:采用免疫组织化学技术检测94例良恶性肾上腺嗜铬细胞瘤组织标本中HSP90和STAT3的表达差异,同时用蛋白免疫印迹法检测24例手术标本中HSP90和STAT3的表达差异,并分析两者联合诊断恶性嗜铬细胞瘤的效用。结果:HSP90和STAT3在恶性嗜铬细胞瘤中阳性表达率分别为66.67%和83.33%,在良性嗜铬细胞瘤中的阳性表达率分别为22.37%和26.32%,在正常肾上腺髓质组织中无表达,恶性嗜铬细胞瘤组与良性嗜铬细胞瘤组之间HSP90和STAT3的表达均存在显著性差异(P=0.001,P0.001);Western Blot分析结果显示HSP90和STAT3在恶性嗜铬细胞瘤中的蛋白表达水平远高于良性嗜铬细胞瘤。联合HSP90和STAT3诊断恶性嗜铬细胞瘤时阳性预测值为0.70。结论:HSP90和STAT3在恶性嗜铬细胞瘤中的表达高于良性嗜铬细胞瘤组织,且联合HSP90和STAT3可有效诊断恶性嗜铬细胞瘤。     

子宫内膜癌热休克蛋白70、90的表达及其临床意义

目的 :探讨子宫内膜癌中热休克蛋白 ( HSP) 70、90的表达及意义。方法 :用免疫组化 Envision法及图象分析仪检测了 3 0例正常子宫内膜、3 0例增生过长子宫内膜和 53例子宫内膜癌中 HSP70、90的表达情况。结果 :子宫内膜癌中 HSP70的表达为( 2 0 9.0 6± 5.3 6 ) ,明显高于正常内膜 ( 1 45.2 1± 4.0 9)和增生过长内膜 ( 1 48.59± 4.2 3 ) ,P均 <0 .0 1 ;子宫内膜癌中 HSP90的表达为 ( 1 6 6 .98± 5.71 ) ,明显低于正常子宫内膜( 2 0 8.57± 3 1 .1 4)和增生过长子宫内膜 ( 2 49.73± 4.94) ,分别为 P<0 .0 5、P<0 .0 1。子宫内膜癌中 HSP70表达随肿瘤病理分级升高而增强 ( P<0 .0 1 ) ,非内膜样癌较内膜样癌表达增强 ( P<0 .0 1 ) ;子宫内膜癌中 HSP90表达随肿瘤病理分级升高而表达减弱 ( P<0 .0 1 ) ,非内膜样癌较内膜样癌表达减弱 ( P<0 .0 1 )。但子宫内膜癌中 HSP70、90表达与肌层浸润深度、术后病理分期、淋巴结转移未见显著相关性 ( P>0 .0 5)。结论 :HSP70、90可能与子宫内膜癌发生及预后有关     

热休克蛋白27和糖调节蛋白78分布异常对心脏移植后血管病变的影响

目的 观察移植后心脏组织中热休克蛋白27(HSP27)和糖调节蛋白78(GRP78)的组织分布,探讨移植后心脏血管病变(CAV)的发病机制.方法 建立大鼠同基因(n=8)和异基因(n=8)心脏移植的Ono模型,采用免疫组织化学法[链霉菌抗生物素蛋白-过氧化物酶(SP)法]验证移植后心脏组织中HSP27和GRP78的组织分布.结果 同基因植组,HSP27和GRP78在心脏组织内均匀分布;异基因移植组,HSP27和GRP78在环血管周围心肌组织中高表达(2.24±0.36比1.04±0.10,P＜0.01;1.51±0.12比0.85±0.30,P＜0.05),而在增生的冠状动脉组织内几乎不表达(2.24±0.36比0.25±0.08,P＜0.01;1.51±0.12比0.16±0.10,P＜0.01).结论 HSP27和GRP78在异基因移植后心脏组织中分布不均,导致冠状动脉组织无力对抗免疫损伤,诱发血管平滑肌细胞过度增殖可能是CAV发生、发展的重要原因.     

Carbon dioxide laser induction of heat shock protein 70 synthesis: Comparison with high temperature treatment

In a previous study, it was demonstrated that heat shock protein 70 (hsp70) was induced by short duration (<1 s) carbon dioxide (CO₂) laser radiation (10.6m. To further characterize the stress response after laser irradiation, the time course of synthesis and cellular localization of hsp70 has been followed. As it had been shown that laser irradiation elevated the temperature to about 67±2 C, the authors also attempted to duplicate the response with high temperature elevation by dipping cells grown on plastic coverslips into media heated in a hot water bath to specified temperatures. Exposure to CO₂ laser irradiation resulted in a time course and localization response similar to that reported for induction of hsp70 by elevated temperature (41–44 C). However, in contrast to the response to elevated temperature, only hsp70 was induced by laser irradiation. Short exposure (1–4 s) of cells medium heated to 58 C produced a response similar to that obtained with CO₂ laser irradiation suggesting that the CO₂ laser irradiation effect on cells is produced by heating for short periods to 55–70 C.The opinions and assertions contained herein are the private views of the authors and are not to be construed as official nor do they reflect the views of the Department of the Army or the Department of Defense (AR 360-5).     

Effects of high peak airway pressure on the expression of heat shock protein 70 in rat lungs: a preliminary study

BACKGROUND: Heat shock protein 70 (HSP70) is induced by a wide variety of stresses in addition to hyperthermia. Recent studies have clarified that mechanical stretching and pressure overload can induce HSP70 in some tissues and cells. However, it remains unclear whether HSP70 is induced in stretch-subjected lungs, such as those under mechanical ventilation. This study was designed to investigate the effects of high peak airway pressure (PAP) ventilation on HSP70 expression in intact rat lungs. METHODS: Male Sprague-Dawley rats were randomly allocated to one of three groups: non-ventilated (anesthesia alone) control group; PAP 15 cm H(2)O group (P15); and PAP 30 cm H(2)O group (P30). The rats in the PAP groups were subjected to pressure-controlled assisted ventilation at the appropriate PAP for 30 min. Rats were killed at 12, 24 and 48 h after ventilation or anesthesia alone, and the lungs were removed. The lung tissues were processed for immunohistochemical and Western blotting analyses of HSP70. RESULTS: Following 30 min of pressure-controlled assisted ventilation, HSP70 expression in the P30 group was significantly up-regulated in bronchiolar cells and subepithelial tissues at 12 h, and this up-regulation continued throughout the observation period. In contrast, there were no significant differences between the control and P15 groups, although the expression of HSP70 was higher in the P15 group than in the control group at all time points. CONCLUSIONS: HSP70 was induced by high PAP ventilation, but its specific role and induction mechanism remain unclear. Therefore, further investigations should be encouraged.     

肝脏移植后的免疫损伤与热休克蛋白的表达

目的 探讨肝脏移植后的免疫损伤与几种主要分子伴侣(热休克蛋白)表达状况之间的内在规律。方法 34份移植后肝脏穿刺标本和10份正常肝脏标本，分为A(无排斥反应)组、B(轻／中度急性排斥反应)组、C(重度急性排斥反应)组、D(慢性排斥反应／肝纤维化)组、E(对照)组。进行HSP60、HSP70、HSP90、HO—1等四种分子伴侣免疫组织化学分析和图像分析。结果 B和C组各指标间无统计学差异，A、D、E与B、C组间有统计学差异。HSP60在移植肝脏中表达降低，排斥反应发生时高；HSP70和HSP90在移植肝脏中升高。HO—1肝脏移植后升高。结论 不同种类的热休克蛋白依据自身表达的特点对移植后的免疫损伤作出反应，体现了细胞的自我保护机制。     

热休克转录因子1蛋白在人肝细胞癌组织中的表达及临床意义

目的 探讨热休克转录因子1( HSF1)蛋白在人肝细胞癌组织中的表达及临床意义,并推测HSF1在肝细胞癌发生、发展中的可能分子机制.方法 收集2006年3月至2007年3月第四军医大学西京医院67例行手术切除的肝细胞癌组织,以及21例因肝血管瘤行手术切除的部分正常肝脏组织,采用免疫组织化学法柃测肝细胞癌及正常肝脏组织中HSF1蛋白及热休克蛋白70( HSP70)的表达,分析HSF1蛋白与患者临床病理特征及预后之间的关系,并根据HSFI蛋白与HSP70表达情况的相关性分析推测HSF1在肝细胞癌发生、发展中的可能分子机制.不同组织中HSF1蛋白阳性率的分析以及肝细胞癌中HSF1蛋白阳性表达率与各临床病理资料的关系采用x2检验及Fisher确切概率法,HSFI蛋白与HSP70在肝细胞癌中表达的相关性采用Spearman相关性分析.采用Kaplan-Meier法绘制生存曲线,生存情况比较采用Log-rank检验.结果 HSFI蛋白在肝细胞癌组织中的阳性率为69％ (46/67),在正常肝脏组织中的阳性率为29％ (6/21),两者比较,差异有统计学意义(x2=10.628,P＜0.05).HSP70在肝细胞癌组织中的阳性率为57％( 38/67),在正常肝脏组织中的阳性率为24％ (5/21),两者比较,差异有统计学意义(x2=6.929,P＜0.05).HSF1蛋白与HSP70在肝细胞癌组织中的表达呈正相关(r=0.319,P＜0.05).HSFI蛋白的高表达与肝细胞癌的包膜完整与否、分化程度以及TNM分期有关(X2=5.935,9.762,5.159,11.267,P＜0.05);而与患者性别、年龄、HBsAg水平、AFP水平以及是否存在门静脉癌栓无关(x2=0.822,0.172,2.059,P＞0.05).HSF1蛋白阳性和阴性表达者的生存时间分别为(21.4+1.9)个月和(29.8±2.7)个月,两者生存率比较,差异有统计学意义(x2=4.276,P＜0.05).结论 HSF1与肝细胞癌的发生、发展、侵袭转移以及不良预后相关,其可能通过调控HSP70的表达而发挥作用,在肝细胞癌的诊断和治疗中有良好应用前景.