朱丹溪“倒仓法”探析

“倒仓法”是朱丹溪在《格致余论》中所记载的中医特色疗法,此法单用黄牛肉配合特殊的熬制和服用方法,用以治疗各种停痰瘀滞导致的无名奇病,同时有延年益寿的功效。但如今关于这一古法的研究和实践甚少,笔者通过查阅古代中医文献,结合现代医学的部分观点,探析“倒仓法”的独特之处及作用机制。“倒仓法”实施的关键在于黄牛肉、长流水、“强饮之”、轮回酒等,其作用机制可能与肌肽的抗氧化、抗衰老、防治慢性病的作用以及肠道微生态中致病菌减少、益生菌大量繁殖有关。     

Protective effects of carnosine alone and together with alpha-tocopherol on lipopolysaccharide (LPS) plus ethanol-induced liver injury

The aim of this study was to investigate the effect of carnosine (CAR) alone and together with vitamin E (Vit E) on alcoholic steatohepatitis (ASH) in rats. ASH was induced by ethanol (3 times; 5 g/kg; 12 h intervals, via gavage), followed by a single dose of lipopolysaccharide (LPS; 10 mg/kg; i.p.). CAR (250 mg/kg; i.p.) and Vit E (200 mg d-α-tocopherol/kg; via gavage) were administered 30 min before and 90 min after the LPS injection. CAR treatment lowered high serum transaminase activities together with hepatic histopathologic improvements in rats with ASH. Reactive oxygen species formation, malondialdehyde levels, myeloperoxidase activities and transforming growth factor β1 (TGF-β1) and collagen 1α1 (COL1A1) expressions were observed to decrease. These improvements were more remarkable in CAR plus Vit E-treated rats. Our results indicate that CAR may be effective in suppressing proinflammatory, prooxidant, and profibrotic factors in the liver of rats with ASH.     

Carnosine and anserine as modulators of neutrophil function

Carnosine and anserine, the bioactive peptides found in most meats and fish, were tested for their ability to modulate neutrophil and U937 cell function, specifically with respect to respiratory burst, interleukin-1β production and apoptosis. Both peptides increased the respiratory burst and interleukin-1β production of human neutrophils but not of U937 cells. They suppressed apoptosis of human neutrophils but enhanced apoptosis of U937 cells as assessed by DNA strand breaks. These results suggest that carnosine and anserine have the capacity to modulate the immune response at least in human neutrophils.     

肌肽对环磷酰胺毒性影响的初步研究

目的研究肌肽减少环磷酰胺毒性的效果。方法连续15天给小鼠注射环磷酰胺和肌肽，定期检测小鼠的体重，白细胞和红细胞及骨髓细胞的变化情况，并记录60天内小鼠的存活数。15天后取小鼠肝脏，测丙二醛的含量。结果肌肽明显提高了小鼠的白细胞和骨髓细胞的数目，降低了丙二醛的含量，并延长了小鼠的生存期，但对小鼠的体重没有改善作用。结论肌肽对环磷酰胺的毒性有一定的缓解作用。     

肌肽对H9N2亚型猪流感病毒诱导的小鼠急性肺损伤的抗氧化效果

 目的：探讨肌肽（carnosine）对H9N2亚型猪流感病毒（H9N2-SIV）诱导的急性肺损伤（ALI）肺组织抗氧化的效果。方法：选用6～8 周龄SPF级雌性BALB/c小鼠150只,随机分为对照组、模型组和肌肽干预组,每组50只,分别给予正常鸡胚尿囊液、H9N2-SIV和肌肽+H9N2-SIV。实验第2、4、6、8和14天,每组分别处死8只小鼠,观察肺组织的病理变化,测定肺组织匀浆中丙二醛（MDA）的含量、超氧化物歧化酶（SOD）和髓过氧化物酶（MPO）的活性及肺湿/干重比值（W/D）。结果：肌肽可减轻H9N2-SIV造成的小鼠临床症状,降低死亡率。肌肽干预于第6、8天明显改善了肺组织的水肿程度(W/D降低,P＜0.05）并减轻了肺部的病理变化;实验至第6、8天可见肺组织MDA含量显著降低（P＜0.05）,SOD活性显著提高（P＜0.05）;于实验第4、第6和第8天可见肺组织MPO活性显著降低（P＜0.05,P＜0.01）。结论：肌肽可改善H9N2-SIV感染后肺组织的水肿程度,降低肺组织MDA含量和MPO活性,提高SOD活性,抑制自由基和脂质过氧化反应,从而减轻小鼠肺损伤的程度,降低死亡率。     

Biological functions of histidine-dipeptides and metabolic syndrome

The rapid increase in the prevalence of metabolic syndrome, which is associated with a state of elevated systemic oxidative stress and inflammation, is expected to cause future increases in the prevalence of diabetes and cardiovascular diseases. Oxidation of polyunsaturated fatty acids and sugars produces reactive carbonyl species, which, due to their electrophilic nature, react with the nucleophilic sites of certain amino acids. This leads to formation of protein adducts such as advanced glycoxidation/lipoxidation end products (AGEs/ALEs), resulting in cellular dysfunction. Therefore, an effective reactive carbonyl species and AGEs/ALEs sequestering agent may be able to prevent such cellular dysfunction. There is accumulating evidence that histidine containing dipeptides such as carnosine (β-alanyl-L-histidine) and anserine (β-alanyl-methyl-L-histidine) detoxify cytotoxic reactive carbonyls by forming unreactive adducts and are able to reverse glycated protein. In this review, 1) reaction mechanism of oxidative stress and certain chronic diseases, 2) interrelation between oxidative stress and inflammation, 3) effective reactive carbonyl species and AGEs/ALEs sequestering actions of histidine-dipeptides and their metabolism, 4) effects of carnosinase encoding gene on the effectiveness of histidine-dipeptides, and 5) protective effects of histidine-dipeptides against progression of metabolic syndrome are discussed. Overall, this review highlights the potential beneficial effects of histidine-dipeptides against metabolic syndrome. Randomized controlled human studies may provide essential information regarding whether histidine-dipeptides attenuate metabolic syndrome in humans.     

硅烷化玻璃酸酯在皮肤抗皱剂中细胞水平的功能研究

硅烷化玻璃酸酯复合物(silanol hyaluronate compound,SHAC)是一种透明质酸衍生物。类人胶原和肌肽是当前市场上主流的抗皱成分。本研究将SHAC用于皮肤抗皱剂中,研究其对成纤维细胞的影响。SHAC分别与类人胶原和肌肽复配,作用于体外培养的L929细胞,检测正常细胞的增殖活性和UVB损伤细胞的修复能力。结果表明:(1)肌肽能促进L929细胞的增殖,具有抑制UVB照射细胞引起的氧化损伤的能力。类人胶原蛋白没有明显效果。(2)SHAC分别与类人胶原、肌肽制备复配制剂,均能够显著促进细胞的增殖,抑制UVB照射引起的细胞损伤。SHAC能增强类人胶原和肌肽的功效,在开发皮肤抗皱功能的产品领域前景良好。     

On the mechanisms of ageing suppression by dietary restriction-is persistent glycolysis the problem?

The mechanism(s) by which dietary restriction (DR) suppresses ageing and onset of age-related pathologies are discussed in relation to frequency of glycolysis, and the reactivity of glycolytic intermediates. Most glycolytic intermediates are potentially toxic and readily modify (i.e. glycate) proteins and other macromolecules non-enzymically. Attention is drawn to the reactivity of methyglyoxal (MG) which is formed predominantly from the glycolytic intermediates dihydroxyacetone- and glyceraldehyde-3-phosphates. MG rapidly glycates proteins, damages mitochondria and induces a pro-oxidant state, similar to that observed in aged cells. It is suggested that because DR animals' energy metabolism is less glycolytic than in those fed ad libitum, intracellular MG levels are lowered by DR The decreased glycolysis during DR may delay senescence by lowering intracellular MG concentration compared to ad libitum-fed animals. Because of the reactivity MG and glycolytic intermediates, occasional glycolysis could be hormetic where glyoxalase, carnosine synthetase and ornithine decarboxylase are upregulated to control cellular MG concentration. It is suggested that in ad libitum-fed animals persistent glycolysis permanently raises MG levels which progressively overwhelm protective processes, particularly in non-mitotic tissues, to create the senescent state earlier than in DR animals. The possible impact of diet and intracellular glycating agents on age-related mitochondrial dysfunction is also discussed.     

Carnosine protects against NMDA-induced neurotoxicity in differentiated rat PC12 cells through carnosine-histidine-histamine pathway and H(1)/H(3) receptors

Since the histidine-containing dipeptide carnosine (beta-alanyl-L-histidine) is believed to have many physiological functions in the brain, we investigated the neuroprotective effects of carnosine and its mechanisms of action in an in vitro model of neurotoxicity induced by N-methyl-d-aspartate (NMDA) in differentiated PC12 cells. Pretreatment with carnosine increased the viability and decreased the number of apoptotic and necrotic cells measured by MTT and Hoechst 33342 and propidium iodide (PI) double staining assays. Carnosine also can inhibit the glutamate release and increase HDC activity and the intracellular and extracellular contents of carnosine, histidine and histamine detected by high-performance liquid chromatography (HPLC). The protection by carnosine was reversed by alpha- fluoromethylhistidine, a selective and irreversible inhibitor of histidine decarboxylase (HDC). Pyrilamine and thioperamide, selective central histamine H(1) and H(3) antagonists also significantly reversed the protection of carnosine. Further, the inhibition of glutamate release by carnosine was reversed by thioperamide. Therefore, the protective mechanism of carnosine may not only involve the carnosine-histidine-histamine pathway, but also H(1)/H(3) receptors and the effective inhibition of glutamate release. This study indicates that carnosine may be an endogenous protective factor and calls for its further study as a new antiexcitotoxic agent.     

Short-duration β-alanine supplementation increases training volume and reduces subjective feelings of fatigue in college football players

The purpose of this study was to examine the effect of 30 days of β-alanine supplementation in collegiate football players on anaerobic performance measures. Subjects were randomly divided into a supplement (β-alanine group [BA], 4.5 g·d⁻¹ of β-alanine) or placebo (placebo group [P], 4.5 g·d⁻¹ of maltodextrin) group. Supplementation began 3 weeks before preseason football training camp and continued for an additional 9 days during camp. Performance measures included a 60-second Wingate anaerobic power test and 3 line drills (200-yd shuttle runs with a 2-minute rest between sprints) assessed on day 1 of training camp. Training logs recorded resistance training volumes, and subjects completed questionnaires on subjective feelings of soreness, fatigue, and practice intensity. No difference was seen in fatigue rate in the line drill, but a trend (P = .07) was observed for a lower fatigue rate for BA compared with P during the Wingate anaerobic power test. A significantly higher training volume was seen for BA in the bench press exercise, and a trend (P = .09) for a greater training volume was seen for all resistance exercise sessions. In addition, subjective feelings of fatigue were significantly lower for BA than P. In conclusion, despite a trend toward lower fatigue rates during 60 seconds of maximal exercise, 3 weeks of β-alanine supplementation did not result in significant improvements in fatigue rates during high-intensity anaerobic exercise. However, higher training volumes and lower subjective feelings of fatigue in BA indicated that as duration of supplementation continued, the efficacy of β-alanine supplementation in highly trained athletes became apparent.