关龙胆地上部分保肝作用研究

目的通过不同毒物引起的肝损伤来研究关龙胆地上部分的保肝作用。方法选用D-半乳糖胺、硫代乙酰胺、四氯化碳等3个肝损伤毒物造肝损伤模型,通过不同机制引起的肝损伤来研究关龙胆地上部分的保肝作用。结果关龙胆地上部分有一定的保肝作用,可降低各种肝损伤模型的ALT,AST,AKP等。结论关龙胆地上部分也有一定的药用价值,用全草取代地下部分入药有一定的可行性。     

模拟医学生物化学实验血清标本的探讨

用蛋白胨、三油酸甘油酯、鼠肝、葡萄糖等材料模拟血清标本,通过测定该血清中蛋白、血脂、谷丙转氨酶、血糖以及部分物理参数,探讨了模拟血清从外观和实验项目上满足实验教学的可行性。结果表明,模拟血清实用、简便易得,既能解决医学生物化学实验教学标本来源困难问题,又能防止实验室污染和节省大量实验经费。     

Morphologic evaluation of the liver in hereditary angioedema patients on long-term treatment with androgen derivatives

17 alpha-Alkylated androgens are highly effective in preventing attacks in HAE patients. These drugs, however, seem to be implicated in the development of cholestatic jaundice, peliosis hepatis, and liver tumors. In order to assess the risk-benefit balance of the long-term therapy with androgen derivatives, a follow-up investigation was performed in 13 HAE patients. The results of this study indicate that long-term treatment (15 to 47 mo) with low doses of danazol or stanozolol does not induce significant hepatic damage detectable by laboratory tests or liver biopsy. However, the limited number of patients, although in a rather long period of observation, still suggests a careful control and the use of minimal effective doses.     

Growth,regression and cell death in rat liver as related to tissue levels of the hepatomitogen cyproterone acetate

Previous studies have shown that xenobiotic compounds such as the environmental pollutant -hexa-chlorocyclohexane (-HCH) and the synthetic sex steroid cyproterone acetate (CPA) induce growth of rat liver by hypertrophy and hyperplasia. After withdrawal of the growth stimuli, liver hypertrophy was usually found to be readily reversible. Conflicting observations were made concerning the fate of liver hyperplasia: hepatic hyperplasia persisted when induced by -HCH but was found to be partially reversible when induced by CPA. The present study confirms the reversibility of hepatic hyperplasia induced by CPA in rats: about 30% of liver DNA present at maximal liver enlargement disappeared within 6 days after cessation of CPA treatment. Simultaneously, a dramatic increase in the rate of cell elimination by apoptosis was found. Glutamate-pyruvate transaminase and alkaline phosphatase in serum did not show major increases, suggesting that cell death was not due to lytic membrane damage. Furthermore, if treatment with CPA was continued or resumed, the enhanced DNA content persisted and the number of apoptotic bodies was greatly reduced. These observations suggest that the occurrence of cell death is due to withdrawal of the growth stimulus CPA. It may reflect a regulatory phenomenon serving to maintain homeostasis of cell number.Further studies showed that CPA is rapidly eliminated from rat liver and serum: t 1/2 in the liver is about 11 h. In contrast, -HCH was previously found to be eliminated more slowly: t 1/2 approximately 144 h. The present study revealed that -HCH, CPA and nafenopin lower the number of apoptotic bodies. This suggests that inducers of liver growth can inhibit hepatocellular death by apoptosis. It is concluded that the regression of hyperplasia after CPA withdrawal may be due to its rapid elimination. On the other hand the relatively long persistence of -HCH may result in inhibition of cell death and thereby stabilize hepatic hyperplasia.Abbreviations CPA cyproterone acetate - -HCH -hexachlorocyclohexane - PB phenobarbital - NAF nafenopin - AB apoptotic body - b.w. body weight - p. admin. post-administration - GPT glutamate-pyruvate transaminase - ALP alkaline phosphatase Dedicated to Professor W. Koransky on the occasion of his 65th birthday     

犬失血性休克早期血浆3种酶活性值的变化

用１０只犬复制失血性休克模型,观察休克前、休克３０ｍｉｎ及回输血后３０ｍｉｎ时,血浆中心肌相关酶—肌酸激酶（ＣＫ）、谷草转氨酶（ＧＯＴ）、α－羟丁酸脱氢酶（ＨＢＤ）活性值的变化。结果发现：失血性休克３０ｍｉｎ时,ＣＫ、ＧＯＴ较休克前显著下降（Ｐ＜０．０５,Ｐ＜０．０１）;ＨＢＤ值也下降,但无统计学意义（Ｐ＞０．０５）。输血后３０ｍｉｎ时,ＣＫ、ＧＯＴ、ＨＢＤ值回升,与休克３０ｍｉｎ时比显著升高（Ｐ＜０．０５）,与休克前比无显著性差别（Ｐ＞０．０５）。提示：失血性休克早期心肌细胞可能存在有一种保护性反应,心肌细胞没有发生明显损伤。     

Lipidomics investigation of reversal effect of glycyrrhizin (GL) towards lithocholic acid (LCA)-induced alteration of phospholipid profiles

Context: Glycyrrhizin (GL), the major ingredient isolated from licorice, exerts multiple pharmacological activities.

Objective: To elucidate the protective mechanism of GL towards lithocholic acid (LCA)-induced liver toxicity using lipidomics.

Materials and methods: GL (200?mg/kg) dissolved in corn oil was treated intraperitoneally for 7?d. On the 4th day, 200?mg/kg LCA was used to treat mice (i.p., twice daily) for another 4?d. The protective role of GL towards LCA-induced liver toxicity was investigated through evaluating the liver histology and the activity of alanine transaminase (ALT). The complete lipid profile was employed using UFLC-Triple TOF MS-based lipidomics.

Results: Intraperitoneal (i.p.) administration of 200?mg/kg GL can significantly protect LCA-induced liver damage, indicated by alleviated histology alteration and prevention of the ALT elevation. Lipidomics analysis can well separate the control group from LCA-treated group, and three lipid components were major contributors, including LPC 16:0, LPC 18:0, and LPC 18:2. GL treatment can significantly prevent LCA-induced reduction of these three lipid compounds, providing a new explanation for GL's protection mechanism towards LCA-induced liver toxicity.

Discussion and conclusion: The recent study highlights the importance of lipidomics in elucidating the therapeutic mechanism of herbs.     

Re-evaluation of serum alanine aminotransferase upper normal limit and its modulating factors in a large-scale population study.

BACKGROUND: The upper normal limit (ULN) of serum alanine-aminotrasferase (ALT) normal range was recently challenged, because patients diagnosed with liver diseases may have 'normal' or near-'normal' ALT levels, and because possible modulators are often ignored in determining normal range. AIM: To estimate the ULN for serum ALT and to identify factors modulating it. SUBJECTS AND METHODS: We reviewed medical records of subjects aged 15-90, who underwent standard panels of laboratory tests, including serum ALT, over 6 months at a central laboratory. Three groups were defined: Group 1, comprised total study population (N=272 273). Group 2 (N=87 020) comprised total study population, excluding those receiving potentially hepatotoxic drugs, or diagnosed with liver disease, or had any abnormal laboratory test results other than for triglycerides, cholesterol, glucose, or HbA1c. Group 3 (N=17 496) the 'healthy' population, from whose ALT values we established the new ULN, comprised Group 2 subjects with normal triglycerides, cholesterol, glucose, and HbA1c levels. RESULTS: The 95th percentile ALT values, corresponding to the ULN, in groups 1, 2, and 3 were 50.1, 40, and 37.5 U/l, respectively. 6.2% (16 943/273 273) of subjects whose ALT was below ULN listed by the test manufacturer (52 U/l), had ALT level above our new ULN. Linear and logistic-regression analyses showed that ALT levels were significantly modified by gender, age, glucose, cholesterol, triglycerides, and overweight/obesity diagnosis. Significant interaction was found between gender, glucose and cholesterol levels. CONCLUSIONS: In this first large-scale study of 'healthy' population, serum ALT ULN was far lower than currently accepted value. Age and gender may be considered when determining the ULN for ALT.     

ALT持续正常的HBeAg阴性慢性HBV感染者临床特征

目的 分析ALT持续正常的HBeAg阴性慢性HBV感染者临床特征。 方法 回顾性收集60例2013年9月—2020年1月于延安大学附属医院感染病科门诊就诊的ALT持续正常HBeAg阴性慢性HBV感染者。比较患者基线和随访终点各指标的差异,统计随访结束时患者HBV DNA、HBsAg自然转阴以及肝炎活动、肝硬化和肝癌的累计发生率。计量资料两组间比较采用配对t检验或Wilcoxon符号秩和检验。 结果 所有患者随访24.00~72.00月,其中31例患者在随访过程中行肝组织活检,18例（58.1%）患者肝脏伴有轻度损伤,13例（41.9%）患者肝脏存在中度损伤。患者的HBsAg、HBeAb、HBcAb、ALT和ALB水平随访前和随访后差异均有统计学意义（P均<0.05）,而HBV DNA、AST和LSM水平差异均无统计学意义（P均>0.05）。随访结束时6例患者检测不到HBV DNA;4例患者出现HBsAg自然阴转;2例患者出现肝炎活动;2例患者发展为肝硬化;1例患者进展为肝细胞癌。 结论 约30.0%的ALT持续正常HBeAg阴性慢性HBV感染者有抗病毒治疗指征。此类患者如果条件允许应积极行肝组织活检评估肝脏损伤程度;临床医生也可以根据患者的病毒学、影像学和人口学特征直接给予抗病毒治疗。