Expression of Hepatocyte Growth Factor and c-Met Receptor in Gastric Mucosa during Gastric Ulcer Healing

Background: Ethanol is generally believed to inhibit extracellular Ca 2+ influx, thereby inhibiting gastric muscle contraction. Recently, we observed that verapamil inhibited only the amplitude of spontaneous phasic contractions, whereas ethanol inhibited both amplitude and frequency. In our objective to investigate the mechanism of ethanol's inhibition of gastric motility, the involvement of various protein kinases in ethanol-inhibited spontaneous phasic contractions of the stomach muscle strips was tested. Methods: Circular muscle strips (2.0 × 0.2 cm) were prepared from the corpus of cat stomach in order to measure isometric contraction in a chamber filled with Krebs-Ringer solution (pH 7.4, temperature 36 °C) bubbled with 5% CO 2 in O 2. Results: Spontaneous phasic contraction was not affected by various receptor antagonists (1 μM atropine, 1 μM hexamethonium, 1 μM phentolamine and 1 μM propranolol) or 1 μM tetrodotoxin. EGTA and verapamil dose-dependently inhibited only the amplitude of spontaneous phasic contractions and not the frequency. Ethanol dose-dependently inhibited both the amplitude and frequency of phasic contractions. The amplitude and frequency of spontaneous phasic contractions were significantly inhibited by protein kinase C and tyrosine kinase inhibitors. However, neither protein kinase C activator nor various phosphatase inhibitors blocked the inhibitory effect of ethanol. Conclusions: Ethanol appears to inhibit spontaneous phasic contractions by a mechanism other than the inhibition of protein kinase C or tyrosine kinase or the inhibition of extracellular Ca 2+ influx.     

重组人肝细胞生长因子激活因子质粒的构建、表达和功能研究

背景:肝细胞生长因子激活因子(HGFA)是活化单链前体HGF(pro-HGF)成为有生物学功能的HGF的关键酶.在受损组织器官的修复和再生中发挥重要作用。目的:制备rhHGFA-Fc融合蛋白并证实其具有肝细胞保护功能。方法:采用基因重组技术构建表达人源化HGFA成熟肽段与人IgG Fc段融合蛋白的载体,以脂质体介导法转染人胚肾293细胞。纯化293细胞表达产物,以蛋白质印迹法鉴定纯化蛋白(rhHGFA-Fc融合蛋白)及其对pro-HGF的酶切活性,以流式细胞术检测融合蛋白介导的肝细胞凋亡抑制作用。结果:SDS-PAGE显示转染重组质粒的293细胞总蛋白纯化产物在62 kDa处显示单一蛋白条带。蛋白质印迹法结果显示纯化的rhHGFA-Fc融合蛋白能与抗hHGFA单克隆抗体发生特异性反应,并将pro-HGF酶切为α链和β链,酶切活性呈剂量依赖性,半效酶切活性(IC_(50))为8.22 nmol/L;流式细胞术结果显示融合蛋白通过激活pro-HGF发挥其抑制肝细胞凋亡的作用。结论:293细胞表达的rhHGFA-Fc融合蛋白纯度高、酶切活性强,可高效激活pro-HGF,对于肝组织严重损伤,特别是肝硬化基础上肝损伤的治疗具有潜在价值。     

原发性高血压患者肝细胞生长因子、血管紧张素Ⅱ、内皮素的变化及苯那普利的干预作用

目的:探讨原发性高血压(EH)患者血清肝细胞生长因子(HGF)及血管紧张素Ⅱ(AngⅡ)、内皮素(ET)的浓度与原发性高血压进展的关系及苯那普利对其生成的影响.方法:以20例健康人做对照(正常对照组),另选择1、2级原发性高血压患者40例(为1级原发性高血压组18例,2级原发性高血压组22例),分别采用酶联免疫吸附法和放射免疫法测定苯那普利治疗前及治疗6周后血清中HGF、AngⅡ和ET浓度.结果:1、2级原发性高血压组治疗前血清HGF、ET和AngⅡ水平明显高于正常对照组(P＜0.05～0.01);并与平均动脉压呈正相关(r分别为0.568、0.460、0.623);血清HGF与ET、AngⅡ亦有良好相关性(r分别为0.512、0.563).治疗后血压下降,同时血清HGF、ET和AngⅡ水平较治疗前明显下降(P＜0.05).结论:HGF、AngⅡ及ET水平与高血压有关.苯那普利在降压的同时能降低HGF及AngⅡ、ET水平.     

Possible role of nerve growth factor in the pathogenesis of alcohol dependence

BACKGROUND: Recent studies have raised the possibility that nerve growth factor (NGF) is abnormally regulated in the central nervous system (CNS) of animal models of chronic ethanol treatment. The goals of this study were to determine whether prolonged alcohol consumption is associated with the plasma NGF levels and to assess the effect of a positive family history of alcohol dependence on plasma NGF levels in the alcohol-dependent patients. METHODS: We used the enzyme-linked immunosorbent assay (ELISA) to determine the concentrations of peripheral NGF in patients with alcohol dependence and in a control group. RESULTS: The plasma NGF concentrations in the alcohol-dependent patients were significantly lower than in the controls (71.9 vs 110.5 pg/mL, respectively). Moreover, the alcohol-dependent patients with positive family histories showed a greater decrease in their NGF levels than those subjects with negative family histories (64.7 vs 83.3 pg/mL, respectively). CONCLUSIONS: Our study suggests that the NGF levels may be a trait marker for the development of alcohol dependence.     

Glucose metabolism, insulin-like growth factor-I, and insulin-like growth factor-binding protein-1 after alcohol withdrawal

Alcohol abusers often present with deteriorated glucose metabolism and insulin resistance. Changes in other glucoregulators, such as insulin-like growth factor-I (IGF-I) and IGF-binding protein-1 (IGFBP-1) may also be related to alcohol abuse. We studied the effects of alcohol withdrawal on blood glucose, serum insulin and C-peptide, and plasma IGF-I and IGFBP-1 levels in 27 noncirrhotic male alcoholics aged 43 +/- 9.0 (mean +/- SD) years on four consecutive days immediately after withdrawal. A 4-day monitoring period was conducted in four healthy nonalcoholic control men. The groups were similar in age and body mass index. Glucose, insulin, IGF-I, and IGFBP-1 did not differ significantly between the groups at the baseline, but C-peptide was higher in alcoholics (p < 0.01). After alcohol withdrawal, serum insulin and C-peptide levels increased in close correlation with each other (r = 0.82, p < 0.001). During the 4-day observation period in alcoholics, IGFBP-1 levels declined by 59%, whereas IGF-I increased by 41% (p < 0.001 for both comparisons). The change in insulin correlated inversely with the change in IGFBP-1 levels (r = -0.39, p < 0.05). In the control group, glucose, insulin, IGF-I, and IGFBP-1 remained unchanged during the 4-day monitoring period, whereas some reduction was observed in C-peptide. In conclusion, alcohol withdrawal enhances insulin production, as seen in increased C-peptide levels. An inverse correlation between the changes in insulin and that in IGFBP-1 might suggest that inhibition of IGFBP-1 by insulin remains largely unchanged during the acute phase of alcohol withdrawal.     

肝细胞生长因子对小鼠实验性结肠炎结肠细胞因子的影响

背景：肝细胞生长因子（HGF）是一种多功能因子,近年文献报道其有可能成为炎症性肠病（IBD）的辅助治疗药物。目的：研究HGF对小鼠实验性结肠炎结肠细胞因子的影响,探讨HGF用于IBD辅助治疗的可能机制。方法：30只健康昆明小鼠随机分为正常对照组、结肠炎模型组和HGF干预组,后两组以嗯唑酮溶液灌肠诱导结肠炎模型。造模后予HGF干预组小鼠HGF100μg／d腹腔注射,连续4d。评估各组疾病活动指数（DAI）,第13d处死所有小鼠,观察结肠大体和组织学损伤情况．以荧光定量聚合酶链反应（PCR）检测结肠黏膜白细胞介素（IL）-4、IL-5、IL-10、干扰素（IFN）-γ和肿瘤坏死因子（TNF）-αmRNA表达。结果：与正常对照组相比,结肠炎模型组的DAI和结肠大体、组织学损伤评分以及结肠黏膜IL-4、IL-5、IL-10、IFN-γ、TNF-αmRNA表达量显著增高（P〈0．01）;HGF干预组上述指标均较结肠炎模型组显著降低（P〈O．01）,与正常对照组相比无明显差异。结论：HGF可能通过抑制结肠黏膜细胞因子的表达,改善小鼠实验性结肠炎的结肠炎症反应。     

溃疡性结肠炎结肠黏膜修复中HGF,c-Met,EGFR的作用

目的:观察并分析肝细胞生长因子(HGF)及其受体c-Met与表皮生长因子受体(EGFR)在溃疡性结肠炎(UC)活动和非活动阶段患者结肠黏膜的表达情况,探讨其表达的临床意义．方法:根据改良Williams疾病活动指数(DAI) 将42例UC患者分为活动期(n=25)和非活动期(n=17)2组,对照组(n=20)为门诊健康体检者或肠易激综合征患者．结肠镜下活检各组患者结肠黏膜组织,采用免疫组化SABC法检测各组患者结肠黏膜HGF及c-Met表达;SP法检测EGFR及增殖细胞核抗原(PCNA)表达．结果:对照组、活动期UC患者、非活动期 UC患者HGF阳性表达率分别为22％,88％, 100％(X2=62．84,P<0．01);c-Met阳性表达率分别为25％,92％,100％(X2=62．34,P<0．01); EGFR阳性表达率分别为25％,92％,1 00％(X2 =54．34,P<0．01);PCNA过表达率分别为0, 36％,100％(X2=67．50,P<0．01),组间比较差异显著．HGF,c-Met和EGFR在UC患者结肠黏膜表达与PCNA过表达正相关(r=0．648,0．645, 0．565,P<0．01)．结论:HGF,c-Met,EGFR及PCNA在非活动期UC患者结肠黏膜中的表达较活动期UC患者和对照组明显增加．HGF及其受体c-Met与 EGFR在UC患者结肠炎症黏膜修复过程中可能起一定作用．     

HGF质粒体内表达诱导脐血干细胞向肝系细胞分化

目的:观察肝细胞生长因子(hepatocyte growth factor,HGF)作用下,脐血干细胞在体内向肝细胞分化的情况．方法:HGF的裸DNA质粒通过尾静脉快速注入6-8周龄的非肥胖糖尿病／重症联合免疫缺陷(NOD／SCID)小鼠体内,酶联免疫吸附法 (ELISA)检测外周血中HGF水平．收集足月妊娠产妇的脐血,磁式分选法选出CD34 造血干细胞(hematopoietic stem cell,HSC)．20 μL四氯化碳(carbon tetrachloride,CCl4)腹腔注射建立NOD／SCID小鼠急性肝损伤模型,分别输注 CD34 HSC和／或HGF质粒,观察其对死亡率、肝功能恢复的影响,并检测小鼠肝组织内的人源性细胞．结果:快速注入HGF质粒后,体内HGF水平明显上升．实验各组存活率及肝功能恢复情况无明显差异．病理切片显示,联合应用 HGF HSC的实验组,其肝组织损伤程度最轻, 单独应用HGF或HSC的两个实验组结果类似, 对照组最重．在两组注射HSC的小鼠肝组织中,均可检测到人源性的、分泌白蛋白的肝样细胞,且联合应用HGF的实验组中,此种细胞更多,分布更广．结论:HGF可以促进脐血干细胞向肝细胞分化,并发挥肝细胞功能．     

Oxygen dependency of epidermal growth factor receptor binding and DNA synthesis of rat hepatocytes

Background/Aims: Changes in oxygen availability modulate replicative responses in several cell types, but the effects on hepatocyte replication remain unclear. We have studied the effects of transient nonlethal hypoxia on epidermal growth factor receptor binding and epidermal growth factor-induced DNA synthesis of rat hepatocytes.Methods: Lactase dehydrogenase activity in culture supernatant, intracellular adenosine triphosphate content, ²⁵I-epidermal growth factor specific binding, epidermal growth factor receptor protein expression, and ³H-thymidine incorporation were compared between hepatocytes cultured in hypoxia and normoxia.Results: Hypoxia up to 3 caused no significant increase in lactate dehydrogenase activity in the culture supernatant, while intracellular adenosine triphosphate content decreased time-dependently and was restored to normoxic levels by reoxygenation (nonlethal hypoxia). Concomitantly, ¹²⁵I-epidermal growth factor specific binding to hepatocytes decreased time-dependent (to 54.1% of normoxia) and was restored to control levels by reoxygenation, although ¹²⁵I-insulin specific binding was not affected. The decrease in ¹²⁵I-epidermal growth factor specific binding was explained by the decrease in the number of available epidermal growth factor receptors (21.37±3.08 to 12.16±1.42 fmol/10⁵ cells), while the dissociation constant of the receptor was not affected. The change in the number of available receptors was not considered to be due to receptor degradation-resynthesis, since immunodetection of the epidermal growth factor receptor revealed that the receptor protein expression did not change during hypoxia and reoxygenation, and since neither actinomycin D nor cycloheximide affected the recovery of ¹²⁵I-epidermal growth factor binding by reoxygenation. Inhibition of epidermal growth factor-induced DNA synthesis after hypoxia (to 75.4% of normoxia by 3 h hypoxia) paralleled the decrease in ¹²⁵I-epidermal growth factor binding.Conclusions: Transient hypoxia, which caused no increase in lactase dehydrogenase leakage but affected intracellular adenosine triphosphate levels, did, however, modulate the number of available epidermal growth factor receptors without affecting the receptor protein expression, and inhibit the epidermal growth factor-induced DNA synthesis of hepatocytes. This suggests that even transient nonlethal hypoxia affects the epidermal growth factor-induced DNA synthesis of rat hepatocytes through reversible changes in the epidermal growth factor receptor molecule, which depends on oxygen availability.     

Human Hepatocyte Growth Factor in Alcoholic Liver Disease: A Comparison with Change in α-Fetoprotein

To evaluate the hepatic regenerative response in patients with alcoholic liver disease, sera from 263 patients with severe alcoholic hepatitis and/or cirrhosis were analyzed for hepatocyte growth factor (HGF) and α-fetoprotein (AFP). HGF concentration was elevated above healthy controls in 95% of the patients (median level = 2.4 ng/ml), whereas AFP tended to be depressed below controls (median level = 4.1 ng/ml). Correlations with parameters of liver injury (i.e., ascites, encephalopathy, AST bilirubin, and protime) all showed a more significant correlation with HGF concentrations than those of AFP. Patients with HGF levels below the mean (4 ng/ml) exhibited significantly better survival (median survival = 35 months vs. 8.5 months for those with HGF ≥4 ng/ml; p = 0.007). Serum HGF levels were associated with various specific histologic features of alcoholic hepatitis that included, but were not exclusively related to, necrosis.     

Markers of oxidative stress and systemic vasoconstriction in pregnant women drinking > or =48 g of alcohol per day

Background: The precise pathway by which alcohol causes the characteristic features of fetal alcohol spectrum disorders is unknown. Proposed mechanisms for fetal injury from maternal alcohol use include cellular damage from oxidative stress and impaired fetal oxygenation related to maternal systemic vasoconstriction. Our objective was to compare the levels of urinary markers of oxidative stress and systemic vasoconstriction between women consuming large amounts of alcohol during pregnancy and women who did not drink alcohol during pregnancy. Methods: Pregnant women consuming ≥48 g alcohol per day (n = 29) on average and pregnant women who abstained from alcohol use (n = 39) were identified using detailed interviews and home visits. Random maternal urine specimens were collected. Urinary levels of the oxidative stress marker, 8‐isoprostane F2α, and of the vasoactive prostaglandin metabolites, 2,3‐dinor‐6‐keto‐prostaglandin F1α (a vasodilator) and 11‐dehydro‐thromboxane B2 (a vasoconstrictor), were measured using mass spectrometric methods. All analyte levels were corrected for urinary creatinine. Results: In crude analyses, there was no significant difference in 8‐isoprostane F2α between pregnant drinkers and nondrinkers (2.16 vs. 2.08 ng/mg creatinine, respectively, p = 0.87). There were no significant differences between the drinking and nondrinking groups in levels of 2,3‐dinor‐6‐keto‐prostaglandin F1α (1.03 vs. 1.17 ng/mg creatinine, repectively, p = 0.50), 11‐dehydro‐thromboxane B2 (0.72 vs. 0.59 ng/mg creatinine, respectively, p = 0.21), or the ratio of vasodilatory metabolite to vasoconstrictive metabolite (1.73 vs. 2.72, respectively, p = 0.14). Adjusting for maternal age, marital status, smoking, and gestational age at sampling did not substantially alter the results. Conclusion: Our results show no difference in levels of urinary eicosanoid markers of oxidative stress and systemic vasoconstriction between pregnant women who drink heavily and pregnant women who abstain. These findings speak against a role for maternal oxidative stress or systemic vasoconstriction in the pathogenesis of alcohol damage to the fetus.     

Decreased plasma brain-derived neurotrophic factor levels in patients with alcohol dependence

BACKGROUND: Many reports have suggested possible relationships between brain-derived neurotrophic factor (BDNF) and alcohol dependence. A protective effect of BDNF against ethanol-induced cell damage has been suggested, and this effect may contribute to the development or maintenance of alcohol dependence. This study was carried out in order to verify the significance of BDNF in alcohol dependence. METHODS: Peripheral BDNF levels were measured in alcohol-dependent patients and control subjects using an enzyme-linked immunosorbent assay. A physician's interview and standardized questionnaire were used to obtain information regarding each patient's history of alcohol consumption. RESULTS: The mean BDNF level was lower in the alcohol dependence group (389.5 +/- 501.7 pg/ml) than in the normal controls (822.5 +/- 420.7 pg/ml) by analysis of covariance (ANCOVA) (F = 25.79, p < 0.01). The mean BDNF level was lower in the alcohol-dependent patients with a positive family history of alcohol dependence (247.6 +/- 289.2 pg/ml) than in those with a negative family history of alcohol dependence (583.9 +/- 652.8 pg/ml) by ANCOVA (F = 6.51, p = 0.01). The BDNF levels did not correlate significantly with any of the variables analyzed in this study, including Beck depression inventory, state and trait anxiety inventory (STAI-S and T), and various drinking behaviors. CONCLUSIONS: Changes in the levels of BDNF might play a role in the pathophysiology and inheritance of alcohol dependence.     

Impact of alcohol exposure after pregnancy recognition on ultrasonographic fetal growth measures

BACKGROUND: More than 3 decades after Jones and Smith (1973) reported on the devastation caused by alcohol exposure on fetal development, the rates of heavy drinking during pregnancy remain relatively unchanged. Early identification of fetal alcohol exposure and maternal abstinence led to better infant outcomes. This study examined the utility of biometry for detecting alcohol-related fetal growth impairment. METHODS: We obtained fetal ultrasound measures from routine ultrasound examinations for 167 pregnant hazardous drinkers who were enrolled in a brief alcohol intervention study. The fetal measures for women who quit after learning of their pregnancies were compared with measures for women who continued some drinking throughout the course of their pregnancies. Because intensity of alcohol consumption is associated with poorer fetal outcomes, separate analyses were conducted for the heavy (average of >or=5 drinks per drinking day) alcohol consumers. Fetal measures from the heavy-exposed fetuses were also compared with measures from a nondrinking group that was representative of normal, uncomplicated pregnancies from our clinics. Analyses of covariance were used to determine whether there were differences between groups after controlling for influences of gestational age and drug abuse. RESULTS: Nearly half of the pregnant drinkers abstained after learning of their pregnancies. When women reportedly quit drinking early in their pregnancies, fetal growth measures were not significantly different from a non-alcohol-exposed group, regardless of prior drinking patterns. Any alcohol consumption postpregnancy recognition among the heavy drinkers resulted in reduced cerebellar growth as well as decreased cranial to body growth in comparison with women who either quit drinking or who were nondrinkers. Amphetamine abuse was predictive of larger cranial to body growth ratios. CONCLUSIONS: Alterations in fetal biometric measurements were observed among the heavy drinkers only when they continued drinking after becoming aware of their pregnancies. Although the reliance on self-reported drinking is a limitation in this study, these findings support the benefits of early abstinence and the potential for ultrasound examinations in the detection of fetal alcohol effects.     

人胎盘绒毛组织造血因子的测定及对胚胎期造血的意义

目的:为进一步证实胎盘的造血功能,直接了解胎盘绒毛组织中多种造血生长因子开始出现的时间及随胎龄的增长其含量的变化,探讨其对胎盘造血的意义。方法:分别取早孕(40～56d)、中孕(16～22周)、足月妊娠(37～40周)胎盘绒毛组织2g各30份,用生理盐水冲洗3遍,加等量生理盐水制成1∶1胎盘组织匀浆,以3000r/min离心20min,取上清液进行测定。结果:①早期妊娠开始,各种造血细胞生长因子均已产生;②FLT3、白细胞介素3含量在早孕时含量低,随着胎龄增加,胎盘绒毛组织中含量逐渐增加,以晚孕时含量增加明显,各胎龄组间比较,均P<0.01,差异有统计学意义,提示造血活动随着胎龄增加而增强;③干细胞因子、白细胞介素6亦随着胎龄增加其含量逐增,以中、晚孕期含量为高,但两组之间差异无统计学意义;④促红细胞生成素在晚孕期含量最高,提示红系造血因子在晚期妊娠造血活动中起主导作用;⑤血小板生成素、粒细胞集落刺激因子含量在各孕龄间差异无统计学意义。结论:本研究所测的7种造血因子在胎盘造血活动均发挥作用,尤以FLT3配体、白细胞介素3、干细胞因子、白细胞介素-6最为重要。     

皮下脂肪和胎盘的抵抗素表达及与胰岛素抵抗的关系

目的探讨抵抗素与胰岛素抵抗(IR)、肥胖和糖尿病的关系。方法于2003-032004-12选取武汉协和医院正常人腹部(n=12)、腿部(n=8)、妊娠妇女腹部(n=12)皮下脂肪组织和胎盘(n=12)为标本,以Western blot法检测抵抗素蛋白表达情况,测定血糖、血脂、胰岛素、体重、身高,计算IR指数、体重指数(BMI)、体内脂肪百分比(BF%)。结果妊娠妇女胎盘组抵抗素蛋白(67905±8441)(OD值)的表达明显高于妊娠腹部组(40718±3818)(P<0·01);正常人腹部组(39421±6087)(P<0·01)、腿部组皮下脂肪组织(14942±6706)(P<0·001);妊娠腹部组和正常人腹部组皮下脂肪组织均明显高于腿部组(P<0·001);抵抗素蛋白与BMI、IR指数、BF、空腹血糖呈正相关性。结论胎盘可分泌抵抗素,抵抗素与中心性肥胖有密切关系,可能引起IR,导致肥胖、2型糖尿病和妊娠糖尿病。     

肝细胞生长因子及其受体与胃癌

肝细胞生长因子(HGF)是一种多功能的细胞因子,原癌基因c-met编码的蛋白c-Met是HGF的主要受体,HGF与上皮或内皮细胞上的c-Met结合,导致细胞分裂或分化增加,细胞分离,运动能力增强,细胞连接消失。近年研究表明,HGF可影响肿瘤的生长、侵袭和肿瘤新生血管形成,HGF/c-Met与胃癌的发生、发展、转移及预后有着密切的关系。     

肝细胞生长因子对小鼠轻症急性胰腺炎影响的实验研究

及时、有效地控制轻症急性胰腺炎可防止其向重症急性胰腺炎演变，因而具有重要的临床价值。近年来，肝细胞生长因子(HGF)能否减轻啮齿动物的急性胰腺炎正日益受到关注：目的：观察外源性HGF能否减轻小鼠轻症急性胰腺炎，并探讨其作用机制。方法：以雨蛙肽腹腔注射诱发小鼠轻症急性胰腺炎，在制模前和制模中予各组小鼠皮下注射不同浓度的重组人HGF(rhHGF)，部分小鼠同时皮下注射抗rhHGF、单抗。根据血清淀粉酶、脂肪酶水平、胰腺组织学炎症评分和胰腺超微结构的变化评估炎症程度，并测定胰腺匀浆中花生四烯酸代谢产物血栓素(TX)B2和6-酮(keto)-前列腺素(PG)Fla的水平。结果：与单纯炎症组相比，给予4μg／kg或20μg／kg rhHGF小鼠的血清淀粉酶、脂肪酶水平和胰腺组织学炎症评分显著降低，胰腺匀浆中TXB2水平显著降低，6-keto-PGFla。水平显著增高，但4μg／kg与20μg／kg rhHGF。的疗效无显著差异。给予rhHGF。的同时给予抗rhHGF单抗，小鼠的上述各项参数与单纯炎症组无显著差异。结论：外源性HGF能减轻雨蛙肽诱导的小鼠轻症急性胰腺炎，其机制可能与对花生四烯酸代谢的影响有关。抗HGF。单抗能抵消HGF的生物学作用。