Erythropoietin promotes hepatic regeneration after extended liver resection in rats

Background and Aim:  It has been proven in various animal studies that recombinant human erythropoietin (rHuEPO) protects renal, cardiac and neuronal, as well as hepatic, tissue from ischemia, and promotes regeneration of adult central nervous system neurons. To date, no data are available as to whether rHuEPO has the ability to stimulate liver regeneration after liver resection.
Methods:  Rats undergoing 70% or 90% hepatectomy received an intraportalvenous administration (i.p.) of rHuEPO prior to resection or a subcutaneous injection (s.c.) for 3 days postoperatively, control animals were treated with surgery and saline injection only. Regeneration capacity of remnant livers was studied over 7 days by histology and immunohistochemistry (Ki-67, proliferating cell nuclear antigen [PCNA]). Polymerase chain reaction was carried out to measure transforming growth factor β (TGF-β), hypoxia induced factor (HIF), signal transducing activator 3 and vascular endothelial growth factor.
Results:  Ten-day survival in rats undergoing 90% hepatectomy significantly increased in i.p.-pretreated animals. After 70% hepatectomy the mitotic index was significantly increased in both rHuEPO-treated groups. These data were confirmed by PCNA and Ki-67 expression, which was significantly increased in the treated groups 24 h and 2 days after liver resection. TGF-β and HIF mRNA both were upregulated in control animals 3 h after surgery.
Conclusion:  rHuEPO effectively increased liver regeneration in rats after 70% liver resection and enhanced survival after 90% hepatectomy. Thus, rHuEPO may increase the regenerative capacity after major hepatectomy.     

Effects of Bicyclol on Liver Regeneration After Partial Hepatectomy in Rats

Bicyclol is a synthetic antihepatitis drug with antioxidative property. The present study was performed to investigate the effect of bicyclol on liver regeneration after partial hepatectomy in rats. Bicyclol (300 mg/kg) was given to rats subjected to 70% hepatectomy three times before operation. At 6, 24, and 48 h after resection, samples were collected for the measurement of serum alanine aminotransferase (ALT), total bilirubin (TBil), hepatic glycogen, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH). Moreover, liver regeneration rate, proliferating cell nuclear antigen (PCNA) labeling, proliferation index, and histopathological examination were evaluated at 48 h after hepatectomy. As a result, bicyclol significantly increased regeneration rate, mitotic index (MI), PCNA labeling index, and proliferation index in PH rats. Additionally, bicyclol remarkably inhibited the elevation of serum ALT and TBil levels, alleviated the formation of liver MDA, restored impaired antioxidant SOD and GSH, increased hepatic glycogen content, and also attenuated hepatic vacuolar degeneration. These results suggested that bicyclol had a beneficial effect on liver regenerative capacity of the remnant liver tissue after hepatectomy, probably due to its antioxidative property.     

非酒精性脂肪肝大鼠部分肝切除术后肝再生功能的变化

目的 探讨大鼠非酒精性脂肪肝（NAFLD）部分肝脏切除术后肝再生功能的变化。方法 80只Wistar大鼠，随机分为正常对照组（C组，35只）与NAFLD组（F组，45只），C组给予正常饮食喂养，F组给予高脂饲料喂养。在喂养至第12周时行70％肝切除术，两组动物分别于术后0、1、12、24、36h处死，取出残肝，计算再生肝重比；光镜下计数核分裂肝细胞；透射电镜观察术后肝细胞超微结构的变化；免疫组织化学染色法检测增殖细胞核抗原阳性表达率；半定量逆转录聚合酶链反应检测细胞周期蛋白D1的表达变化。结果 光镜和电镜观察显示F组肝窦狭窄迂曲，细胞质内大量脂滴沉积，细胞核小，细胞器少，能量代谢及细胞增殖均不活跃。F组术后12、24、36h核分裂相计数明显低于C组同时相点（P〈0．01）；F组术后再生肝重比、S期细胞分数及增殖指数也较C组下降，差异有统计学意义（P〈0．01）；F组增殖细胞核抗原阳性率、细胞周期蛋白D1的mRNA表达在术后12、24、36h均明显低于C组同时相点（P〈0．01）。结论 中至重度NAFLD大鼠部分肝切除术后DNA合成高峰滞后，肝再生延迟，再生进程主要被阻滞在细胞周期的G1／S期调控点。     

Effect of dietary fat to produce non-alcoholic fatty liver in the rat

Background and Aim:  Non-alcoholic steatohepatitis (NASH) belongs to a spectrum of non-alcoholic fatty liver disease (NAFLD). Oxidative stress is hypothesized to play an important role in the progression of the disease. We used the Lieber/DeCarli model for NASH to investigate the mechanisms involved in its progression.
Methods:  Male Sprague–Dawley rats were fed standard (35% of energy from fat) or high fat (71% of energy from fat) liquid diets, ad libitum or two-thirds of the amount consumed ad libitum initially for 3 weeks and then extended to 5 weeks.
Results:  Steatosis was absent in rats at 3 weeks feeding, but by 5 weeks, the high fat/ad lib group showed microvesicular steatosis and foci of macrovesicular steatosis without inflammation. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were not different. By 5 weeks feeding, hepatic triglycerides were highest in the high fat ad lib group and the ad lib groups were higher compared with their restricted groups. The oxidative stress marker, hydroxyalkenal (HAE) was decreased in the standard ad lib compared with the high fat ad lib group. Liver mRNA of interleukin-6, haem oxygenase-1, and markers of endoplasmic stress: C/EBP homologous protein (CHOP), glucose responsive protein-78 (GRP78) and spliced X-box DNA binding protein (spliced XBP1) were similar in the ad lib groups.
Conclusions:  Extending the feeding period of the high fat/ad lib diet for 5 weeks placed our rats with Type I to II NAFLD compared to the more progressed Type III state previously obtained after 3 weeks feeding. The milder condition obtained raised the prospect of genetic modifiers present in our rats that resist disease progression.     

Selective suppression of initial cytokine response facilitates liver regeneration after extensive hepatectomy in rats

BACKGROUND/AIMS: After extensive hepatectomy, the cytokine network plays an important role in injury to the remnant liver and subsequent impairment of liver regeneration. Tumor necrosis factor alpha (TNF alpha) and interleukin 1beta (IL-1beta) are thought to be the initial cytokines associated with liver injury as well as with regeneration. We investigated the effect of the suppression of these cytokines on liver function and on liver regeneration after subtotal hepatectomy in rats. METHODOLOGY: Following 90% hepatectomy, rats were divided into two groups. Animals in the FR group received intraperitoneal FR167653, a selective inhibitor of TNF alpha and IL 1beta, while those in the Control group received vehicle only. Liver chemistry and serum levels of TNF alpha and IL-6 were measured serially. Liver specimens were obtained 48 hr after surgery and regenerative activity assessed by proliferating cell nuclear antigen (PCNA) expression and remnant liver weight. RESULTS: The survival rate was significantly better in the FR group (76.4+/-11.7 hrs) than in the Control group (26.8+/-4.3 hrs, p=0.0014). Liver enzyme and blood sugar levels after surgery were higher in the FR group compared to the Control group (p=0.03 or less). Changes in serum levels of both TNF alpha and IL-6 were suppressed in FR group rats after surgery. Microscopically, hepatocellular damage and steatosis was less prominent in FR group livers. PCNA labeling index and residual liver weights were higher in the FR group (p<0.001). CONCLUSIONS: Following extensive hepatectomy in rats, suppression of early cytokine induction improved liver function and facilitated liver regeneration. Suppression of selective cytokine responses could allow extended liver resection and reduced risk of liver failure.     

Role of Ursodeoxycholic Acid in Prevention of Methotrexate-induced Liver Toxicity

Aim Methotrexate (MTX)-induced hepatotoxicity restricts the clinical use of this immunosuppressive drug. In this study, our aim was to research the role of oxidative stress in the hepatic toxicity of MTX and the protective effect of ursodeoxycholic acid (UDCA) in this setting. Methods Wistar type rats (n = 32) were divided into four groups; group-1 as the MTX + UDCA, group-2 as the MTX, group-3 as the UDCA, group-4 as the saline-receiving groups. The MTX + UDCA and MTX groups of rats received 50 mg/kg of UDCA administered orally; whilst physiological saline was administered orally to the MTX and saline groups and continued for the next 6 days. On the second day of the study, the MTX + UDCA and MTX groups had a single intraperitoneal dose of MTX of 20 mg/kg. The UDCA and saline groups also received similar volumes of physiological saline intraperitoneally. On the sixth day, serum samples were collected and analyzed for ALT, alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) and homogenated liver tissues were examined for reactive oxygen metabolites (ROM); luminol, lucigenin, lipid peroxygenation product malondialdehyde (MDA) and glutathione (GSH) levels. Results In the MTX group, serum ALT, ALP, GGT and tissue ROM levels were higher and GSH level was lower. On the histopathological examination, hepatocellular necrosis was clearly more evident in the MTX group than the MTX + UDCA group. Conclusions UDCA treatment protects against MTX-induced liver toxicity. Histopathologically hepatocyte necrosis can be prevented by UDCA treatment, indicating clearly the hepatoprotective effect of this agent on MTX-induced liver injury.     

Beneficial effects of splenectomy on massive hepatectomy model in rats

Aim:  Possible spleno-hepatic relationships during hepatectomy remain unclear. The purpose of this study was to investigate the impact of splenectomy during massive hepatectomy in rats.
Methods:  Rats were divided into the following two groups: 90% hepatectomy (Hx group), hepatectomy with splenectomy (Hx+Sp group). The following parameters were evaluated; survival rate, biochemical parameters, quantitative RT-PCR for hemeoxygenase-1 (HO-1) and tumor necrosing factor α (TNFα), immunohistochemical staining for HO-1, proliferating cell nuclear antigen labeling index and liver weights.
Results:  The survival rate after massive hepatectomy significantly improved in Hx+Sp group as well as serum biochemical parameters, compared with Hx group ( P  < 0.05). HO-1 positive hepatocytes and its mRNA expression significantly increased and TNFα mRNA expression significantly decreased in Hx+Sp group compared with Hx group ( P  < 0.05). Moreover, liver regeneration was significantly accelerated at 48 and 72 h after hepatectomy in Hx+Sp group.
Conclusions:  Splenectomy had beneficial effects on massive hepatectomy by ameliorating liver injuries and promoting preferable liver regeneration.     

Improvement of the survival rate after rat massive hepatectomy due to the reduction of apoptosis by caspase inhibitor

BACKGROUND AND AIM: Acute liver failure after massive hepatectomy is caused by both necrosis and apoptosis in the remnant liver. We investigate the protective effect of the caspase inhibitor on apoptosis after massive hepatectomy in rats. METHODS: Benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (ZVAD-fmk) is a general inhibitor of the caspase. Male Wister rats weighing 200-300 g were divided into three groups: 90Hx group undergoing 90% hepatectomy, 95Hx group undergoing 95% hepatectomy, 95Hx + ZVAD group undergoing 95% hepatectomy and administration of ZVAD-fmk. The 7-day survival rate was studied, and the rats were sacrificed at the 1, 2, 3, 5, and 7th day after hepatectomy. The remnant liver tissues were stained with hematoxylin-eosin, and with proliferating cell nuclear antigen (PCNA) for evaluation of liver regeneration, and with TdT-mediated dUTP-biotin nick end labeling (TUNEL) and in situ oligo ligation method (ISOL) for evaluation of apoptosis. RESULTS: The 7-day survival rates were 100%, 0%, and 30%, in the 90Hx, 95Hx, and 95Hx + ZVAD groups, respectively. There was no significant difference in PCNA labeling index (LI) between the 95Hx and 95Hx + ZVAD groups. TUNEL and ISOL LI of 95Hx + ZVAD group were significantly lower than those of 95Hx group. Fatal liver failure after massive hepatectomy was characterized by more apoptosis and less mitosis of hepatocytes. ZVAD-fmk could significantly attenuate apoptosis of hepatocytes in the remnant liver and improve the survival rate after 95% hepatectomy in rats. CONCLUSION: Caspase inhibitors such as ZVAD-fmk may provide a new adjuvant therapy to treat liver failure after massive hepatectomy.     

Effects of prior splenectomy on remnant liver after partial hepatectomy with Pringle maneuver in rats.

BACKGROUND/AIMS: In the case of the liver resection, the temporary occlusion of the hepatoduodenal ligament (Pringle maneuver) is often used. However, the maneuver causes hepatic ischemia/reperfusion (I/R) injury that strongly affects the recovery of patients. The present study investigated the effects of prior splenectomy on the remnant liver in partial hepatectomized rat with Pringle maneuver. METHODS: Pringle maneuver was conducted just before a two-thirds partial hepatectomy. Efficacy of splenectomy was assessed by survival rate, serum alanine aminotransferase (ALT), neutrophil infiltration into liver, recovery of remnant liver weight, and liver proliferating cell nuclear antigen (PCNA) levels. Ischemic preconditioning was performed as follows; 10 min of total hepatic ischemia followed by 10 min of reperfusion. RESULTS: In partial hepatectomized rats with 30 min of Pringle maneuver, seven out of 12 rats died within 3 days. On the other hand, when splenectomy was performed on 3 days before the maneuver, only one out of 12 rats died. When prior splenectomy was performed on eight and 18 days before the Pringle maneuver, respectively, similar efficacy was observed. In addition, prior splenectomy on 3 days before the maneuver showed that serum ALT activity, neutrophil infiltration, recovery of remnant liver weight, and PCNA levels in partial hepatectomized rats with Pringle maneuver were also ameliorated as compared with those of control rats without splenectomy. When effects of prior splenectomy were compared with those of ischemic preconditioning in these situations, efficacy of prior splenectomy was comparable with that of the ischemic preconditioning. CONCLUSIONS: Prior splenectomy ameliorated the I/R injury in the remnant liver after partial hepatectomy with Pringle maneuver. Effects of prior splenectomy may influence the liver for long duration, because splenectomy on 18 days before the maneuver still exerts effective action.     

Mild hypothermia does not affect liver regeneration after partial hepatectomy in mice

Background: The use of mild hypothermia has been suggested to be therapeutically useful in treating acute liver failure. It is not known if hypothermia influences liver regeneration. Aim: To assess the effect of hypothermia on liver regeneration in mice. Methods: After partial (70%) hepatectomy (PHx), C57BL6/J mice were randomly assigned to either a hypothermic group or a normothermic group. Controlled mild hypothermia was maintained for up to 3 h after surgery. In addition, assessment of liver mass restitution was examined by studying the induction of key cell cycle proteins (cyclin A, D1 and E) and hepatocyte proliferation [assessment of proliferating cell nuclear antigen (PCNA) protein expression] by Western blotting and DNA synthesis by measuring 5‐bromo‐2‐deoxyuridine (BrdU) incorporation by immunohistochemical techniques 45 h after PHx. Results: Partial hepatectomy induced a vigorous proliferative response in the remnant livers of both groups of mice (normothermic and hypothermic groups), as evidenced by the induction of key cyclins, PCNA and incorporation of BrdU after PHx. The liver/body weight ratio and both cyclin and PCNA protein expression as well as BrdU incorporation did not differ between the regenerating livers of hypothermic and normothermic groups. Conclusion: Mild hypothermia does not influence liver regeneration in mice.     

Role of peroxisome proliferator-activated receptor-gamma (PPARgamma) during liver regeneration in rats

Background and Aim:  Peroxisome proliferator-activated receptor-gamma (PPARγ), a member of the nuclear receptor superfamily, is widely expressed in adipocytes and other tissues, including the liver. Several reports have shown that PPARγ activation induced cell-cycle arrest and apoptosis in tumor cells. We investigated the role of the PPARγ/ligand system and the effect of the PPARγ agonist during liver regeneration.
Methods:  Expression of PPARγ and serum levels of 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) by enzyme immunoassay were evaluated in rats following partial hepatectomy (PH group). Further, the effect of the PPARγ agonist, pioglitazone, on liver regeneration (PH + PGZ group) was evaluated by proliferating cell nuclear antigen labeling index, relative liver weight, and expression of cell-cycle regulators.
Results:  The number of PPARγ-stained hepatocytes decreased at 24 h (PH, 15.8 ± 2.2%; sham, 35.5 ± 2.4%; P  < 0.001) and increased in the late phase of liver regeneration compared to the sham-operated group ( P  < 0.001 at 48–120 h). The peaks of serum 15d-PGJ2 (627.0 ± 91.1 pg/ml) and PPARγ expression (90.6 ± 3.1%) coincided in the late phase of liver regeneration. Also, oral administration of pioglitazone inhibited hepatocyte proliferation, in terms of the proliferating cell nuclear antigen (PCNA) labeling index and p27 expression during the late phase of liver regeneration, and caused a transient reduction in liver mass when compared to the PH group.
Conclusions:  These results indicate that the PPARγ/ligand system may be one of the key negative regulators of hepatocyte proliferation and may be responsible for the inhibition of liver growth in the late phase of liver regeneration.     

甜菜碱对酒精性肝损伤大鼠高同型半胱氨酸血症和肝脂质过氧化的影响

目的：观察甜菜碱对大鼠高同型半胱氨酸血症（hyperhomoeysteinemia，HHcy）和肝脏脂质过氧化的作用和影响。方法：将60只SD大鼠随机分为5组（每组12只）：正常对照组，模型组，甜菜碱低、高剂量组，腺苷蛋氨酸（S-adenosylmethionine，SAM）组。除对照组外，其余4组给予酒精、鱼油灌胃配合高脂饮食构建酒精性肝损伤大鼠模型，药物治疗于造模4周后开始，第8周处死全部大鼠，测定血浆总同型半胱氨酸（total plasma homoeysteine，tHcy）浓度、血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、白蛋白（Alb）、白／球蛋白比值（A／G）、肝匀浆丙二醛（MDA）、超氧化物歧化酶（SOD）和还原型谷胱甘肽（GSH）含量，并进行肝脏病理组织学检查。结果：与对照组比较，模型组大鼠tHcy、ALT、AST、MDA含量均明显升高（P〈0．01），SOD、GSH水平明显降低（P〈0．01）。与模型组对比，甜菜碱低、高剂量组大鼠tHcy、ALT、AST、MDA均显著降低（P〈0．01），肝组织SOD含量明显上升（P〈0．01），GSH含量无显著变化（P〉0．05），甜菜碱低、高剂量组之间无明显差异（P〉0．05）；SAM组能显著增加肝组织GSH贮量（P〈0．01），但对血浆tHcy水平无显著影响（P〉0．05），余治疗作用均与甜菜碱治疗无显著差别（P〉0．05）。结论：甜菜碱可防治酒精性肝损伤，其机制可能为降低高同型半胱氨酸血症，改善肝组织脂质过氧化。本文结果显示，甜菜碱的作用优于腺苷蛋氨酸。     

Efficacy and limitation of bone marrow transplantation in the treatment of acute and subacute liver failure in rats

Aim:  Recent reports have shown that bone marrow cells (BMC) retain the potential to differentiate into hepatocytes. Thus, the BMC have been recognized as an attractive source for liver regenerative medicine. However, it has not been clarified whether BMC transplantation can be used to treat liver damage in vivo . In the present study, we explored whether BMC possess therapeutic potential to treat acute and/or subacute liver failure.
Methods:  Fulminant hepatic failure (FHF) was induced by 70% hepatectomy with ligation of the right lobe pedicle (24% liver mass), followed by transplantation of BMC into the spleen. Dipeptidyl peptidase IV-positive (DPPIV⁺) BMC were then transplanted into DPPIV-negative (DPPIV^-) recipients following hepatic irradiation (HIR) in which 70% of the liver was resected and the remnant liver irradiated.
Results:  There was no benefit of BMC transplantation towards survival in the FHF model. DPPIV⁺ hepatocytes appeared in the liver tissues of the DPPIV^- HIR model rats, but DPPIV⁺ hepatocytes replaced less than 13% of the recipient liver.
Conclusion:  BMC transplantation may have limitations in the treatment of fulminant or acute liver failure because they do not have sufficient time to develop into functional hepatocytes. Preparative HIR may be beneficial in help to convert the transplanted BMC into host hepatocytes, and provide a survival benefit. Although, However, the precise mechanism warrants further studies.     

Circulating and liver tissue levels of retinol-binding protein-4 in non-alcoholic fatty liver disease

Aim:  Retinol-binding protein-4 (RBP4) has been proposed as a new adipokine that regulates insulin action in muscles and the liver, and contributes to the pathogenesis of insulin resistance. As non-alcoholic fatty liver disease (NAFLD) is related to insulin resistance, we aimed to evaluate RBP4 levels in the serum and liver of patients with NAFLD.
Methods:  Serum RBP4 was measured in 30 NAFLD patients and 30 matched healthy controls. RBP4 expression in the liver of NAFLD patients was shown by immunohistochemistry.
Results:  Serum RPB4 was significantly lower in NAFLD patients compared with controls (25.15 vs 34.66 µg/mL, P  < 0.001) and there was no correlation with metabolic parameters or insulin resistance. RBP4 liver tissue immunostaining was more extensive and intense in NAFLD liver compared with normal liver and the RBP4 immunohistochemical score was positively correlated with the grade of steatosis, grade of non-alcoholic steatohepatitis activity and stage of fibrosis.
Conclusions:  In NAFLD patients, serum RBP4 was significantly lower as compared with controls and did not correlate with insulin resistance. In contrast, RBP4 liver tissue expression was enhanced and correlated with NAFLD histology.     

姜黄素对大鼠非酒精性脂肪肝的干预作用

[目的]研究姜黄素对大鼠非酒精性脂肪肝的保护作用。[方法]30只Wismr大鼠随机分为对照组、非酒精性脂肪肝模型组和姜黄素干预组。对照组以普通饲料饲养，模型组和干预组给予高脂饲料饲养，干预组每日予50mg／kg姜黄素灌胃，共计12周。实验结束处死大鼠，收集血清和肝组织。检测血清丙氨酸氨基转移酶活性、天冬氨酸氨基转移酶活性和血清总胆固醇含量，以及肝组织γ-谷氨酰转肽酶活性、三酰甘油含量、超氧化物歧化酶活性和谷胱甘肽活性。肝组织行苏木精-伊红染色和油红O染色检测肝脏病理改变。[结果]与模型组比较，干预组能显著降低丙氨酸氨基转移酶、天冬氨酸氨基转移酶和肝组织γ-谷氨酰转肽酶活性，减少血清总胆固醇和肝组织三酰甘油含量；显著升高肝组织超氧化物歧化酶和谷胱甘肽活性；明显减轻大鼠肝内脂肪沉积，改善肝细胞的脂肪性病理改变。[结论]姜黄素通过抗氧化作用，对大鼠非酒精性脂肪肝具有良好的干预作用。     

利拉鲁肽对非酒精性脂肪肝大鼠胰岛素抵抗的改善作用*

目的研究利拉鲁肽对非酒精性脂肪性肝病（NAFLD）大鼠胰岛素抵抗（IR）的改善作用。方法取SD大鼠50只,采用高脂饲料喂养法建立NAFLD大鼠模型,将造模成功的32只大鼠随机分为4组,即模型组(A组,n=8）,其余3组为不同剂量利拉鲁肽处理组,包括B组【0.9 mg·kg-1·d-1,n=8】、C组【（1.8 mg·kg-1·d-1）,n=8】和D组【（3.6 mg·kg-1·d-1,n=8】。在药物干预4 w后,取血和肝脏,制备肝组织匀浆,分别测定大鼠体质量、肝质量、肝指数、血糖、胰岛素（FINS）、血脂（TG、TC）、转氨酶（ALT、AST）、血清丙二醛（MDA）、谷胱甘肽氧化酶（GSH-Px）、肝组织超氧化歧化酶（SOD）、肿瘤坏死因子α（TNF-α）水平。结果与模型组比,药物干预后大鼠体质量、肝指数、血ALT、FINS、FPG、HOMA-IR、MDA和肝组织TG、TC、MDA水平均显著下降（P<0.05）,大剂量组上述指标下降显著高于中小剂量组（P<0.05）;与模型组比,药物干预后大鼠肝组织GSH-Px和SOD水平均显著升高（P<0.05）,且大剂量组升高明显高于中小剂量组（P<0.05）;各组间TNF-α变化无明显差异（P>0.05）。结论利拉鲁肽能显著降低NAFLD大鼠血脂和血糖水平,改善IR,治疗作用呈明显的剂量相关性。     

氧化苦参碱对非酒精性脂肪性肝病大鼠肝脏保护作用研究

目的 观察氧化苦参碱(OMT)干预对非酒精性脂肪性肝病(NAFLD)大鼠肝脏的保护作用。方法 随机将40只SD大鼠分为对照组10只、模型组10只、OMT干预组10只和辛伐他汀干预组10只,采用高脂饮食饲养建立NAFLD模型,自第9 w开始分别给予OMT或辛伐他汀灌胃至16 w。采用ELISA法检测血清白细胞介素-1β(IL-1β)、IL-6、IL-10和肿瘤坏死因子-α(TNF-α)水平。取肝组织匀浆,检测超氧化物歧化酶(SOD)、还原型谷胱甘肽(GSH)和丙二醛(MDA)水平。结果 OMT干预组大鼠体质量和肝质量分别为(610.3±9.4)g和(11.6±0.7)g,显著低于模型组【分别为(631.8±13.9)g和(13.9±0.6)g,P<0.05】;血清ALT和AST水平分别为(78.9±7.0)U/L和(120.4±11.3)U/L,显著低于模型组【分别为(96.7±11.4)U/L和(183.1±25.9)U/L,P<0.05】;血清TC、TG和LDL水平分别为(2.0±0.2)mmo/L、(2.2±0.1)mmo/L和(1.0±0.1)mmo/L,显著低于模型...     

卡托普利对非酒精性脂肪性肝病大鼠肝细胞脂肪变性的影响

目的 研究卡托普利对非酒精性脂肪性肝病(NAFLD)大鼠肝细胞脂肪变性的影响。方法 随机将64只大鼠分为对照组16只(普通饲料喂养和生理盐水灌胃)、模型组16只(高脂饲料和生理盐水灌胃)、卡托普利处理组16只和罗格列酮处理组16只。给药6 w后取血清和肝组织,检测肝组织细胞色素氧化酶P4502E1(CYP2E1)mRNA水平及血清丙二醛(MDA)和谷胱甘肽(GSH)水平。结果 模型组肝细胞体积增大,见广泛性脂肪变性和细胞水肿,而卡托普利处理组大部分肝细胞排列正常,可见少量的脂肪变性,部分细胞水肿;卡托普利处理组血清AST、ALT、TC和TG水平分别为(94.1±15.6)U/L、(27.3±6.2)U/L、(1.4±0.2)mmol/L和(1.0±0.2)mmol/L,显著低于模型组【分别为(134.4±35.1)U/L、(35.2±7.1)U/L、(1.8±0.4)mmol/L和(1.4±0.2)mmol/L,P＜0.05】;卡托普利处理组肝湿重、肝指数和肝组织CYP2E1 mRNA水平分别为(11.7±2.1)g、(2.3±0.3)%和(1.8±0.2),显著低于模型组【分别为(14.3±2.0)g、(2.6±0.2)%和(2.3±0.1),P＜0.05】;卡托普利处理组血清MDA水平为(7.6±2.5)nmol/L,显著低于模型组【(12.1±2.6)nmol/L,P＜0.05】,而血清GSH水平为(41.0±17.5)mg/L,显著高于模型组【(22.2±10.2)mg/L,P＜0.05】。结论 卡托普利可有效减轻非酒精性脂肪性肝病大鼠肝细胞脂肪变性程度,可能与纠正脂代谢紊乱、恢复肝功能、增强抗氧化应激能力有关。     

Beneficial effects of Kampo medicine Inchin-ko-to on liver function and regeneration after hepatectomy in rats.

Aim: Inchin-ko-to (ICKT), Kampo medicine, is known to inhibit hepatocyte apoptosis as well as promote the secretion and excretion of bile. The aim of this study is to clarify the effects of ICKT on liver function and hepatic regeneration after massive hepatectomy in rats. Methods: Male Wistar rats received 2 g/kg ICKT from 3 days preoperatively and underwent 90% hepatectomy. Liver sections were stained using immunohistochemistry (hemeoxygenase-1 [HO-1], alpha-smooth muscle actin [SMA], and proliferating cell nuclear antigen [PCNA]). Results: The survival period was significantly prolonged, and the remnant liver/body weight ratio was significantly increased postoperatively in the ICKT group. The values of transaminase, total bile acid, and total bilirubin were significantly improved in the ICKT group. In the ICKT group, PCNA and HO-1 were strongly expressed early postoperatively, but the expression of alpha-SMA was weak. Conclusion: The preoperative administration of ICKT has been suggested to provide beneficial effects in promoting hepatic regeneration and preventing postoperative hepatic failure. The reduced activation of stellate cells may be involved in their mechanisms.