大鼠肝纤维化肝组织中抗衰老标志蛋白和抗增殖蛋白的表达研究

目的 研究猪血清所致肝纤维化大鼠肝组织中抗衰老标志蛋白(RGN)、抗增殖蛋白(PHB)表达及谷胱甘肽复方注射液(CGII)对其的干预. 方法 健康雄性Wistar大鼠40只,随机分为正常组、造模组.正常组予等渗盐水腹腔注射0.5 ml/只,造模组予腹腔注射无菌猪血清0.5ml/只,每周两次,连续8周,随机处死造模大鼠4只行病理学检查,验证造模成功后,停止注射猪血清,剩余造模组大鼠随机分为纤维化组和CGII干预组.CGII干预组大鼠给予浓度60 mg/mlCGII肌肉注射;正常组和纤维化组均予等单位体质量容积的等渗盐水肌肉注射,每日一次,连续6周.取大鼠肝组织行HE及Masson染色.RT-PCR和免疫组织化学检测肝组织中RGN、PHB mRNA及蛋白质表达. 计量资料采用单因素方差分析,两两比较采用LDS检验,病理学半定量结果采用秩和检验分析. 结果 纤维化组大鼠肝组织RGN、PHB mRNA相对表达量分别为75.99±12.8、64.54±12.35较正常组的182.09±17.84、192.20±17.12明显减低,F值分别为105.646、347.232,P值均＜0.001,差异均有统计学意义;RGN、PHB相对蛋白表达量分别为10.85±2.81、14.5±2.75较正常组的61.08±7.10、55.86±4.23表达均明显降低,F值分别为226.343、525.889,P值均＜ 0.001,差异均有统计学意义.CGII干预后大鼠肝纤维化程度较纤维化组明显减轻(P值均＜ 0.001),肝组织RGN、PHB的mRNA和蛋白表达均较纤维化组明显增高,差异有统计学意义(P值均＜ 0.001).结论 RGN及PHB在猪血清所致大鼠肝纤维化肝组织表达降低.     

Unilateral renal hemodynamics studied by an indicator-dilution technic in man

A method for measuring renal blood flow utilizing a dye curve recorded from the renal vein following the injection of indocyanine green into a renal artery has been evaluated in 29 kidneys of hypertensive patients. The early portion of the downslope of the dye curve could be described by a single exponential, which was distorted later by a changing slope that always corresponded to the expected time of arrival of recirculating dye.

Renal blood flow calculated from the area under the extrapolated dye curve was compared in 11 kidneys with flow measured during ureteral catheterization by the PAH clearance method. Close agreement between the methods was noted in all but one kidney, in which the discrepancy was best explained as a deficiency in the PAH method.

In kidneys supplied by a single renal artery, the smooth curves and exponential downslopes indicate that intrarenal mixing of dye is essentially complete. Apparently accurate flows were measured in those kidneys supplied by separate dorsal and ventral arteries, but slight irregularities in the curves suggest that complete venous mixing does not always occur. In two kidneys with accessory polar arteries, the dye was not adequately mixed and total renal blood flow could not be measured.

Dye curves were utilized to assist in the evaluation of renal artery stenosis in 2 patients. The authenticity of a renal artery pressure gradient measured at the time of catheterization was established in 1 case by demonstrating that the catheter was not impeding renal blood flow. In a second case, a measured pressure gradient was shown to be at least partly factitious because of the prolonged dye curve and low flow obtained with the catheter advanced through the stenosis.

It is suggested that the method may have clinical application for the measurement of separate renal blood flow, particularly when clearance methods cannot be performed. In addition, it offers the opportunity to study the effects of drugs and disease on renal transit time and renal vascular volume in man.     

Insulin uptake by the human alcoholic cirrhotic liver

Insulin uptake by the human cirrhotic liver was studied in six patients with Laennec's cirrhosis, and the result was compared with that found in ten control patients with varying diseases affecting the biliary system. All patients had portal catheters for diagnostic purposes. The fractional hepatic uptake of insulin was calculated from the clearance rates for insulin obtained after a constant rate infusion into a peripheral vein and the portal vein in each patient. The fractional hepatic extraction of insulin was 13% +/- 5 in cirrhotic patients and differed significantly from the fractional hepatic extraction found in controls (51% +/- 5;P less than 0.001).     

Hemodynamics in the isolated cirrhotic liver

Increased intrahepatic resistance is the initial event to the increased portal pressure and development portal hypertension in cirrhosis. Narrowing of the sinusoids due to anatomic changes is the main component of the increased intrahepatic resistance. However, a dynamic component is also involved in the increased vascular tone in cirrhosis. The imbalance between the hyperresponsiveness and overproduction of vasoconstrictors (mainly endothelin-1 and cyclooxygenase-derived prostaglandins) and the hyporesponsiveness and impaired production of vasodilators [mainly nitric oxide (NO)] are the mechanisms responsible of the increased vascular tone in the sinusoidal/postsinusoidal area. In contrast, the vascular resistance in the hepatic artery, which is determined in the presinusoidal area, is decreased due to increased vasodilators (NO and adenosine). This suggests different availabilities of NO in the intrahepatic circulation with preserved production in the presinusoidal area and impaired production in the sinusoidal/postsinusoidal area.     

Amoebic abscess in the cirrhotic liver.

Though amoebic liver abscess and liver cirrhosis occur very commonly in hospital practice in the tropics, they have not to the knowledge of the present authors hitherto been reported to occur simultaneously in the same patient. The patient described here, who had clear-cut clinical and histological features of chronic liver cirrhosis with portal hypertension and ascites, presented somewhat acutely with liver pain and an amoebic liver abscess that contained 'chocolate sauce' on needle aspiration. The amoebic abscess, although, no doubt, superimposed on chronic irreversible cirrhosis, rapidly regressed on metronidazole therapy. The infrequency with which liver abscess and liver cirrhosis coexist cannot be satisfactorily explained. It is probable, however, that extensive scarring in the liver may prevent entamoeba histolytica from thriving.     

UDP glucuronosyltransferase in the cirrhotic rat liver

In patients with cirrhosis, the elimination of drugs metabolized by glucuronidation is relatively preserved, in comparison with the metabolism of drugs by oxidation. This study explores this phenomenon at a molecular level. In cirrhotic rat livers the content of UDP-glucuronosyltransferase (UGT) was examined by immunohistochemistry and immunoblotting using three antibodies: (i) a polyclonal antibody directed against a broad number of UGT isoforms from both family 1 and family 2; (ii) a family 2-specific antibody; and a (iii) family 1-specific antibody. The steady state mRNA level of UGT of a family 2 isoform was also detected by northern blot analysis. The results demonstrate normal or increased UGT protein by immunohistochemistry and immunoblot in cirrhotic livers compared with controls. This was accompanied by increased steady state mRNA encoding the UGT isoform UGT2B1. In contrast, an isoform of cytochrome P450 (CYP2C11) was reduced markedly in both immunohistochemical staining and immunoblot analysis. These results suggest that in cirrhosis there is a comparative increase or at least a maintenance of UGT enzyme content and that this most likely occurs at a pretranslational level.     

Interferon accumulation in cirrhotic rat liver

SUMMARY. In patients with chronic hepatitis C, the therapeutic effect of interferon (IFN) is influenced by the progression of liver disease. In a previous study, we showed that 2',5'-oligoadenylate synthetase activity in the liver homogenate was significantly lower in cirrhotic rats than in controls after injection of murine IFN. To determine the reason for this decrease, we injected IFN into rats with thioacetamide-induced cirrhosis and used microautoradiography with human lymphoblastoid interferon ([¹²⁵I]LyIFN). Accumulation of [¹²⁵I]LyIFN in cirrhotic rat livers was approximately half of that in control rats (2880±900 vs 5770±600mm², P <0.01). In the cirrhotic rat livers there were few grains on the hepatocytes, but many on collagen fibres. These results suggest that binding of IFN to its hepatocyte receptors is hindered in the presence of cirrhosis. The decreased amount of IFN reaching hepatocytes may contribute to the poor responses to IFN seen in patients with cirrhosis.     

Resecting hepatocellular carcinoma in cirrhotic liver

Abstract   Resecting hepatocellular carcinoma (HCC) in a cirrhotic patient is potentially dangerous and recurrence of HCC after operation is high. Our current strategy consists of careful preoperative assessment of liver functions by indocyanine green clearance test, intraoperative techniques to reduce blood loss, and postoperative surveillance and prompt treatment of recurrences. The 5-year overall survival rate of HCC patients after resection is 34.3%, which is comparable with that in patients with normal liver (37.3%) or chronic hepatitis (45.3%).     

Ciliated foregut cyst in cirrhotic liver

We encountered a patient with a ciliated hepatic foregut cyst with accompanying liver cirrhosis, which was hard to distinguish from well-differentiated hepatocellular carcinoma. A lesion 2 cm in diameter was found in the subcapsular region of the medial segment of the liver. It was slightly hypoechoic on ultrasononraphy, of high attenuation on nonenhanced computed tomography (CT), of high intensity on T₁-weighted spin echo images of magnetic resonance imaging (MRI), and of isointensity on T₂-weighted spin echo images. It was not enhanced in the arterial phase images of MRI, and was shown as a complete perfusion defect on CT arterial portography. The cyst was enucleated and found to be filled with bloody mucinous fluid.     

Survival benefit of cirrhotic patients with hepatocellular carcinoma treated by percutaneous ethanol injection as a salvage therapy

BACKGROUND: The therapeutic strategy for cirrhotic patients with hepatocellular carcinoma (HCC) who cannot tolerate surgery or transcatheter arterial chemoembolization (TACE) is uncertain. The safety and efficacy of percutaneous ethanol injection (PEI) as a salvage therapy in such patients is not clear. METHODS: A total of 63 (49 men) HCC patients (mean age 67 +/- 11 years), for whom surgery or TACE was not indicated because of the coexistence of various medical conditions, were enrolled and prospectively studied. Fifty-six (89%) were treated with PEI and 7 were treated with conservative measures. The outcome and the factors that may affect survival were evaluated. RESULTS: During a mean follow-up period of 16 +/- 9 months, 17 (30%) of the patients treated with PEI and 5 (71%) of those treated with conservative measures died (P = 0.045). A total of 16 patient-related and tumor-related variables that may influence the outcome were analyzed. Survival analysis showed that female gender, small (< or = 3 cm) solitary tumor and PEI were associated with a better prognosis (P < 0.05). When using the Cox proportional hazard model, PEI was the only significant independent factor predicting survival (relative risk: 0.3, 95% confidence interval: 0.11-0.86, P = 0.024). The 1- and 2-year survival rates were 85% and 65% for patients treated with PEI compared to 57% and 29% for conservative measures (P = 0.016). CONCLUSIONS: PEI may be a treatment option for cirrhotic patients who have HCC and coexisting contraindications that preclude surgery and TACE. Careful pre-treatment patient selection may effectively prolong the survival.