支链氨基酸肠内营养制剂对肝功能损害鼻饲患者蛋白质代谢的影响

目的观察肝功能损害鼻饲患者使用支链氨基酸肠内营养制剂后对蛋白质代谢的影响。方法将60例肝功能损害的鼻饲患者随机分成治疗组30例及对照组30例,两组均于早期给予鼻饲肠内营养,治疗组给予支链氨基酸肠内营养制剂,对照组给予普通型匀浆膳肠内营养制剂,并观察两组患者治疗前第1天及治疗后第14、30天的血清清蛋白(ALB)变化情况。结果两组ALB变化比较,治疗组明显高于对照组,差异有统计学意义(P0.05)。结论肝功能损害的鼻饲患者早期使用支链氨基酸肠内营养制剂能较快改善蛋白质的营养状况。     

支链氨基酸肠内营养制剂对肝功能损害患者的影响

目的观察肝功能损害患者应用支链氨基酸肠内营养制剂后对肝功能恢复的影响。方法将我院收治的60例肝功能损害患者随机分为治疗组和对照组各30例,两组患者均于早期给予肠内营养,治疗组给予支链氨基酸肠内营养制剂,每天3~4次,每次40~45g;对照组给予普通型匀浆膳肠内营养制剂,每天3~4次,每次40~45g。两组患者分别于治疗前第1天、治疗后第14天及治疗后第30天抽血检查肝功能(谷丙转氨酶、谷草转氨酶)及血清清蛋白(ALB)和Hb等指标。结果两组患者谷丙转氨酶、谷草转氨酶指标比较差异有统计学意义(P0.05),治疗组谷丙转氨酶、谷草转氨酶指标下降明显高于对照组;两组血清清蛋白、Hb比较,治疗组明显高于对照组,差异有统计学意义(P0.05)。结论肝功能损害患者早期使用支链氨基酸能促进肝功能恢复,缩短肝功能恢复时间。     

脐血干细胞移植治疗失代偿期肝硬化的临床疗效

目的:探讨人脐血干细胞(umbilical cord blood stem cell,UCBSC)外周静脉移植治疗失代偿期肝硬化的临床疗效及可行性.方法:20例失代偿期肝硬化患者采用人UCBSC外周静脉移植治疗,治疗后定期观察患者血清转氨酶(ALT、AST)、总胆红素(TBIL)、白蛋白(ALB)、凝血酶原时间(PT)和纤维蛋白原(FIB)水平变化,并观察患者临床症状及体征的改善情况及不良反应.结果:UCBSC移植治疗后2周,各项肝功能指标较治疗前无显著性差异(P＞0.05);治疗后4周,除ALT和AST有所改善外(P＜0.05),其余指标无明显改善;治疗后8周各项肝功能指标均有改善(P＜0.05),12周有显著性改善(P＜0.01).治疗后4周大多数患者的临床症状有明显改善,腹水减少和双下肢浮肿减轻15例(75.0%)、乏力好转16例(80%)、食欲改善13例(65%).UCBSC移植后12周患者总体生存率为90%,其中2例患者分别在UCBSC静脉移植后4周和8周因为肝性昏迷和自发性细菌性腹膜炎而死亡.所有患者均未发现与细胞移植相关的副作用.结论:UCBSC外周静脉移植是治疗失代偿期肝硬化一种安全有效的方法,短期内可以改善失代偿期肝硬化患者肝功能及临床症状,是一种值得推荐的治疗方法.     

血小板输注治疗肝硬化的临床疗效观察

目的:观察血小板灌注治疗对肝硬化患者肝功能的影响。方法:选择10名有血小板减少(血小板计数在50,000至100,000/μl)表现的肝硬化患者(Child-Pugh分级分别为A级或者B级),每周给予10个单位血小板输注治疗,疗程共12周,在给予最后一次治疗后坚持随访9个月。在血小板输注治疗结束后1周、1个月、3个月以及9个月时,应用腹部超声检测腹水、CT观察肝脏肿瘤及肝脏体积并检测患者的肝功能指标,如血清白蛋白、血清胆碱酯酶、谷草转氨酶(AST)、谷丙转氨酶(ALT)、总胆红素以及凝血酶原激活时间。结果:2名患者由于皮肤瘙痒中断血小板输注治疗,2名患者治疗后随访丢失,最后共6名患者的数据纳入研究。在接受完最后一次血小板输注治疗后,6名患者的血小板计数无显著提高。最后一次血小板输注治疗后1个月和3个月复查时,患者的血清白蛋白水平显著升高。治疗后1周,3个月以及9个月时,患者血清胆碱酯酶在均显著增加。结论:尽管血小板输注治疗对一部分患者存在不良反应,但其可显著提高肝硬化患者的一些肝功能指标,可以作为临床治疗肝硬化的新方法深入研究。     

益气法制剂对CCL4所致肝纤维化大鼠TGF-β1/Smad信号通路的影响北大核心CSCD

探讨益气法制剂(黄芪、白术)对CCL4所致肝纤维化大鼠的治疗作用及作用机制。采用腹腔注射40%四氯化碳(CCL4)玉米油溶液联合高脂低蛋白饮食建立肝纤维化模型大鼠。成模后分别给予相应药物灌胃治疗12周。HE、Masson染色法观察肝组织形态学变化,生化分析法检测血清肝功能,酶联免疫吸附法(ELISA)检测血清胶原蛋白含量。RT-q PCR检测肝组织内TGF-β1、TβRⅠ、Smad3、Samd7、α-SMA、HGF mRNA表达。给药治疗后,益气法制剂和秋水仙碱均可减轻大鼠胶原沉积,并可改善大鼠肝功能,其机制与抑制TGF-β1/Smad信号通路有关。     

益气法制剂对CCL4所致肝纤维化大鼠TGF-β1/Smad信号通路的影响

探讨益气法制剂(黄芪、白术)对CCL4所致肝纤维化大鼠的治疗作用及作用机制。采用腹腔注射40%四氯化碳(CCL4)玉米油溶液联合高脂低蛋白饮食建立肝纤维化模型大鼠。成模后分别给予相应药物灌胃治疗12周。HE、Masson染色法观察肝组织形态学变化,生化分析法检测血清肝功能,酶联免疫吸附法(ELISA)检测血清胶原蛋白含量。RT-q PCR检测肝组织内TGF-β1、TβRⅠ、Smad3、Samd7、α-SMA、HGF mRNA表达。给药治疗后,益气法制剂和秋水仙碱均可减轻大鼠胶原沉积,并可改善大鼠肝功能,其机制与抑制TGF-β1/Smad信号通路有关。     

发酵乳对肝硬化失代偿期患者肠黏膜屏障功能的影响

目的 观察发酵乳在改善肝硬化失代偿期患者肠黏膜屏障功能、肝功能及提高患者生活质量方面的作用。方法 选择我院78例确诊为肝硬化失代偿期的患者,随机分成对照组和发酵乳组,其中对照组42例,发酵乳组36例。对照组患者给予常规综合治疗,发酵乳组在常规综合治疗的基础上给予口服发酵乳治疗,在治疗前及治疗4周后分别检测并比较两组患者肠黏膜屏障功能、血清白蛋白、血浆氨水平及慢性肝病问卷评分（CLDQ）的变化。结果 治疗前两组患者肠屏障功能、血清白蛋白、氨水平及CLDQ评分差异无统计学意义（均P>0.05）。治疗4周后,发酵乳组患者血清内毒素、血清二胺氧化酶、D-乳酸及血浆氨水平较治疗前显著降低,较对照组治疗后亦降低（均P<0.05）。发酵乳组患者血清白蛋白水平及部分CLDQ评分较治疗前显著升高,较对照组治疗后亦升高（均P<0.05）。结论 在常规综合治疗的基础上加用发酵乳可调节肝硬化失代偿期患者肠道菌群,改善肠黏膜屏障功能,从而保护肝脏功能,提高患者生活质量。     

超声导入疗法治疗慢性乙型肝炎肝纤维化临床研究

目的：探讨超声导入疗法对乙型肝炎肝纤维化患者进行治疗的临床效果。方法：选择符合诊断标准的慢性乙型肝炎肝纤维化患者52例,随机分为试验组和对照组,各26例。对照组患者给予基本保肝治疗,试验组在对照组的基础上加用黄芪注射液进行超声导入,3个月为1个疗程。观察两组患者治疗前后症状、体征、血清肝纤维化指标、肝功能变化及影像学指标。结果：两组患者症状、体征均有不同程度的改善,差异无统计学意义（P〉0．05）;试验组血清肝纤维化指标明显改善,与对照组比较,差异有统计学意义（P〈0．05）;肝功能及影像学指标的改善更明显（P〈0．01）。结论：超声导入疗法对慢性乙型肝炎肝纤维化具有改善肝功能,减少肝细胞外基质的增生与沉积的效用,能够减轻或延缓肝纤维化的进展。     

益生菌高活菌酸奶联合肠内营养对肝纤维化患者的辅助治疗效果观察

目的 比较观察两种微生态制剂联合肠内营养(EN)对肝纤维化患者的营养效果及肝功能的改善情况。方法 选择104例通过瞬时弹性成像技术(TE)排除肝硬化的慢性肝病患者,并且营养风险筛查2002评分(NRS2002)≥3分,按入院顺序随机数字表法分成观察组(益生菌高活菌数酸奶+EN)54例和对照组(金双歧+EN)50例。两组患者入院后24 h内开始启动肠内营养治疗,观察组每日补充高活菌益生菌酸奶,对照组给予肠内营养液加金双歧口服。对比3周后两组患者胃肠道情况、炎性指标、肝功能各项指标、肝纤维化改善程度及营养状况。结果 观察组与对照组患者在使用益生菌制剂3周后,胃肠道症状均有改善,其中观察组恶心、呕吐、腹胀的改善较对照组恢复程度更好(P<0.05),腹泻、便秘的缓解两组差异不大(P>0.05)。通过血浆炎性指标分析,观察组IL-1β、TNF-α下降较对照组明显(P<0.05),血清ALT、AST、GGT、ALP较治疗前降低明显,与对照组相比血清ALT、GGT、ALP的改善较好,差异均具有统计学意义(P<0.05)。在治疗3周后,肝纤维化指标结果显示,观察组与对照组血清L...     

微生态制剂治疗肝硬化肠功能紊乱患者的临床观察

目的探讨微生态制剂治疗肝硬化肠功能紊乱患者的疗效。方法选择80例肝硬化肠功能紊乱患者,随机分成治疗组和对照组。治疗组:常规保肝治疗加金双歧(4粒/次,2次/d);对照组:常规保肝治疗。疗程均为4周。结果治疗组和对照组相比,腹胀、腹泻、腹部不适症状明显改善,血氨水平降低,血浆内毒素水平下降,2组相比差异有显著性(P<0.05)。结论微生态制剂对于改善肝硬化患者临床症状有肯定的价值,并可降低血氨及血浆内毒素水平,有利于肝功能的改善。     

急性肝损伤时氨基酸代谢变化的研究现状

<正> 肝脏是物质代谢的枢纽,是氨基酸代谢的中心器官,当肝脏由于各种原因发生损伤时,可导致体内复杂的代谢紊乱,尤其是氨基酸代谢的紊乱,这已被大量的动物实验及临床研究所证实。关于肝损伤时氨基酸代谢变化的研究近十年来进展迅速,文献报道很多,一般认为肝损伤时存在有两种类型的血浆氨基酸失衡模式,一是慢性肝损伤的血浆氨基酸失衡模式,另一种就是急性肝损伤时的血浆氨基酸失衡模式。前者以支链氨基酸(Brached chain Amino acid,     

Relationship between anti-fibrotic effect of Panax notoginseng saponins and serum cytokines in rat hepatic fibrosis

The aim of this study was to investigate the relationship between anti-fibrotic effect of Panax notoginseng saponins (PNS) and serum cytokines in rat hepatic fibrosis. Hepatic fibrosis induced by carbon tetrachloride (CCl₄) was studied in animal models using SD rats. Liver index, serum alanine amino transferase (ALT), aspartate amino transferase (AST), transforming growth factor-β1 (TGF-β1), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured, respectively. Liver index and the degree of liver fibrosis were also determined. Our results showed that the levels of ALT, AST and liver index in PNS-treated group were markedly lower than those in model group. PNS therapy also significantly attenuated the degree of hepatic fibrosis, collagen area and collagen area percent in liver tissue. Furthermore, the levels of serum TGF-β1, TNF-α and IL-6 were strikingly reduced in PNS-treated group compared with model group while the production of IL-10 was up-regulated. These findings demonstrate that PNS has certain therapeutic effects on hepatic fibrosis probably by immunoregulating the imbalance between pro-fibrotic and anti-fibrotic cytokines.     

Effects of shark hepatic stimulator substance on the function and antioxidant capacity of liver mitochondria in an animal model of acute liver injury

This study was carried out to investigate whether shark hepatic stimulator substance （HSS） can prevent acute liver injury and affect mitochondrial function and antioxidant defenses in a rat model of thioacetamide （TAA）-induced liver injury. The acute liver injury was induced by two intraperitoneal injections of TAA （400 mg/kg） in a 24 h interval. In the TAA plus shark HSS group, rats were treated with shark HSS （80 mg/kg） 1 h prior to each TAA injection. In this group, serum liver enzyme activities were significantly lower than those in the TAA group. The mitochondrial respiratory control ratio was improved, and the mitochondrial respiratory enzyme activities were increased in the TAA plus shark HSS group. The mitochondrial antioxidant enzyme activities and glutathione level were higher in the TAA plus shark HSS group than in the TAA group. These results suggest that the protective effect of shark HSS against TAA-induced acute liver injury may be a result of the restoration of the mitochondrial respiratory function and antioxidant defenses and decreased oxygen stress.     

Identification and preliminary validation of novel biomarkers of acute hepatic ischaemia/reperfusion injury using dual-platform proteomic/degradomic approaches

Hepatic ischaemia/reperfusion (I/R), a major cause of liver damage associated with multiple trauma, haemorrhagic and septic shock, and liver transplantation, contributes significantly to multiple organ failure. Development of novel sensitive biomarkers that detect early stages of liver damage is vital for effective management and treatment of ischaemic liver injury. By using high-throughput immunoblotting and cation–anion exchange chromatography/reversed-phase liquid chromatography-tandem mass-spectrometry, we identified several hepatic proteins, including argininosuccinate synthase (ASS) and estrogen sulfotransferase (EST-1), which were degraded in the liver and rapidly released into circulation during I/R injury. ASS accumulated in serum within 10 min, reached a steady state at 30 min, and persisted up until 3 h after reperfusion following 30 min of total hepatic ischaemia. EST-1 appeared rapidly in blood and attained maximum within 1 hour followed by a decline at 3 h of reperfusion. No ASS or EST-1 protein was detected in serum of control or sham operated rats. ASS and EST-1 exhibited greater sensitivity and specificity toward I/R liver injury as compared with alanine aminotransferase (ALT), an established marker of hepatocellular necrosis. In contrast, serum ASS and EST-1 were undetectable in rats with chronic alcoholic liver disease, while the levels of ALT protein were significantly increased. In addition, ASS, but not EST-1 or ALT accumulated in blood only 6 h after treatment with hepatotoxic combination of lipopolysaccharide and D-galactosamine. These data demonstrate the utility of ASS and EST-1 as novel sensitive and specific biomarkers of acute liver ischaemic injury for prospective clinical studies.     

Identification and preliminary validation of novel biomarkers of acute hepatic ischaemia/reperfusion injury using dual-platform proteomic/degradomic approaches

Hepatic ischaemia/reperfusion (I/R), a major cause of liver damage associated with multiple trauma, haemorrhagic and septic shock, and liver transplantation, contributes significantly to multiple organ failure. Development of novel sensitive biomarkers that detect early stages of liver damage is vital for effective management and treatment of ischaemic liver injury. By using high-throughput immunoblotting and cation-anion exchange chromatography/reversed-phase liquid chromatography-tandem mass-spectrometry, we identified several hepatic proteins, including argininosuccinate synthase (ASS) and estrogen sulfotransferase (EST-1), which were degraded in the liver and rapidly released into circulation during I/R injury. ASS accumulated in serum within 10 min, reached a steady state at 30 min, and persisted up until 3 h after reperfusion following 30 min of total hepatic ischaemia. EST-1 appeared rapidly in blood and attained maximum within 1 hour followed by a decline at 3 h of reperfusion. No ASS or EST-1 protein was detected in serum of control or sham operated rats. ASS and EST-1 exhibited greater sensitivity and specificity toward I/R liver injury as compared with alanine aminotransferase (ALT), an established marker of hepatocellular necrosis. In contrast, serum ASS and EST-1 were undetectable in rats with chronic alcoholic liver disease, while the levels of ALT protein were significantly increased. In addition, ASS, but not EST-1 or ALT accumulated in blood only 6 h after treatment with hepatotoxic combination of lipopolysaccharide and D-galactosamine. These data demonstrate the utility of ASS and EST-1 as novel sensitive and specific biomarkers of acute liver ischaemic injury for prospective clinical studies.     

S-adenosylmethionine (SAMe) protects against acute alcohol induced hepatotoxicity in mice small star, filled

Although S-Adenosylmethionine (SAMe) has beneficial effects in many hepatic disorders, the effects of SAMe on acute alcohol-induced liver injury are unknown. In the present study, we investigated effects of SAMe on liver injury in mice induced by acute alcohol administration. Male C57BL/6 mice received ethanol (5 g/kg BW) by gavage every 12 hrs for a total of 3 doses. SAMe (5 mg/kg BW) was administrated i.p. once a day for three days before ethanol administration. Subsequent serum ALT level, hepatic lipid peroxidation, enzymatic activity of CYP2E1 and hepatic mitochondrial glutathione levels were measured colorimetrically. Intracellular SAMe concentration was measured by high-performance liquid chromatography (HPLC). Histopathological changes were assessed by H&E staining. Our results showed that acute ethanol administration caused prominent microvesicular steatosis with mild necrosis and an elevation of serum ALT activity. SAMe treatment significantly attenuated the liver injury. In association with the hepatocyte injury, acute alcohol administration induced significant decreases in both hepatic SAMe and mitochondrial GSH levels along with enhanced lipid peroxidation. SAMe treatment attenuated hepatic SAMe and mitochondrial GSH depletion and lipid peroxidation following acute alcohol exposure. These results demonstrate that SAMe protects against the liver injury and attenuates the mitochondrial GSH depletion caused by acute alcohol administration. SAMe may prove to be an effective therapeutic agent in many toxin-induced liver injuries including those induced by alcohol.     

微生态制剂治疗肝源性肠道菌群失调与保肝作用

目的:观察采用常规保肝治疗及或加服乐托尔或加服培菲康来治疗慢性肝病疗效.方法:慢迁肝41例及慢活肝37例,各随机分成三组:A组:常规治疗 乐托尔胶囊,2粒/次,2次/d;B组:常规治疗 培菲康胶囊,3粒/次,3次/d;C组:常规治疗:益肝灵 Vit.C Vit.B Co,各2片/次,3次/d,三组疗程均为2个月.结果:75例完成治疗及复查,失访3例.腹胀、腹泻、肝区不适消失率及ALT、内毒素试验复常率二项三组相比有显著意义(P<0.01).乏力、SB复常率在慢活肝中三组相比有显著意义(P<0.01).总有效率:慢迁肝三组分别为83.3%、69.2%、35.7%;慢活肝三组分别为:63.7%、61.5%、33.3%,三组相比有显著意义(P<0.01).结论:常规保肝治疗加服微生态制剂,不论是死菌及其代谢产物或活菌制剂均有肯定的价值,但死菌制剂具有活菌制剂不具备的优点.     

MFGE8 protects against CCl4-induced liver injury by reducing apoptosis and promoting proliferation of hepatocytes

Milk fat globule-EGF factor 8 (MFGE8) has been reported to play various roles in acute injury and inflammation response. However, the role of MFGE8 in liver injury is poorly investigated. The present research was designed to clarify the expression and function of MFGE8 in carbon tetrachloride (CCl₄)-induced liver injury. Using serum cytokine arrays, we selected a promising cytokine MFGE8 as the candidate in the process of hepatitis-fibrosis-hepatocellular carcinoma (HCC) progression, based on the elevated expression in both hepatic fibrosis and HCC models. We validated the increased expression of MFGE8 in liver tissues and serum samples of acute and chronic CCl₄-induced mice. Immunohistochemistry staining of mouse liver tissues indicated that elevated MFGE8 expression was mainly derived from the injured hepatocytes. In addition, MFGE8 expression in the supernatant of primary hepatocytes was accumulated with prolongation of culture time, and CCl₄ treatment further increased the expression of MFGE8. Moreover, a strong correlation between serum MFGE8 expression and liver transaminase activities suggested that MFGE8 may be a novel candidate in liver injury. Intriguingly, mice pretreated with MFGE8 were protected from CCl₄-induced liver injury through antiapoptosis role in the early stage and proproliferation role in the late stage. MFGE8 reduced apoptosis by inhibiting the activation of IRE1α/ASK1/JNK pathway and promoted proliferation by phosphorylation of ERK and AKT. Moreover, serum MFGE8 expression was increased in hepatitis patients while decreased in liver cirrhosis patients. All the results suggest MFGE8 as a novel marker and promising therapeutic agent of liver injury.     

急性肝损伤大鼠模型的血浆氨基酸代谢变化模式

以Ｄ－氨基半乳糖（Ｄ－Ｇａｌａｃｔｏｓａｍｉｎｅ,Ｄ－ＧａｌＮ）造成急性肝损伤（急性肝炎、急性肝坏死）大鼠模型后、对照观察了急性肝损伤大鼠血浆氨基酸的变化,建立了大鼠急性肝损伤时血浆氨基酸的变化模式并对其发生机理进行了探讨。大鼠血浆氨基酸的测定采用聚酰薄层荧光分析技术,其测定结果是：急性肝炎组,酪氨酸（Ｔｙｒ）、天冬氨酸（Ａｓｐ）、谷氨酰胺（Ｇｌｎ）和鸟氨酸（Ｏｒｎ）升高,精氨酸（Ａｒｇ）下降,其余氨基酸无显著变化。急性肝坏死组,除Ａｒｇ显著下降外,其余所有氨基酸都显著升高,而两组支链氨基酸（ＢＣＡＡ）／芳香族氨基酸（ＡＡＡ）克分子比值均显著下降。