Effects of melatonin on acetylsalicylic acid induced gastroduodenal and jejunal mucosal injury

We evaluated the effects of melatonin on acetylsalicylic acid (ASA) induced gastroduodenal and jejunal mucosal injury. We used 40 postpubertal rats divided randomly into five groups of eight animals. The control group consisted of untreated animals. The Mel group was injected intraperitoneally (i.p.) with 5 mg/kg melatonin. The ASA group was injected i.p. with 200 mg/kg ASA. The ASA + Mel group was injected i.p. with 5 mg/kg melatonin 45 min after administering 200 mg/kg ASA i.p. The Mel + ASA group was injected i.p. with 5 mg/kg melatonin 45 min before administering 200 mg/kg ASA i.p. We found no statistically significant differences in mean histopathological scores in the ASA + Mel group compared to the ASA group. ASA caused shortened villi and loss of the apical villus in the duodenum. The histopathological score was increased and villus height was decreased in the ASA group compared to untreated controls. Treatment with melatonin attenuated the histological damage. In the ASA group, occasional areas showed erosion of villi in the jejunum; however, differences in mean histopathological score in ASA group compared to the other groups were not statistically significant. Malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) activities were measured in stomach, duodenal and jejunum tissue. We found increased MDA activity in both stomach and duodenal tissues in the ASA group compared to the control group (p < 0.05). We found no statistically significant changes in MDA levels in jejunal tissue in the ASA group compared to the control group. We found no change in SOD activity in either stomach or duodenal tissues in the ASA group compared to the control group. We observed decreased SOD activity in jejunal tissue in the ASA group compared to the control group (p < 0.05). We detected no change in GSH activity in stomach, duodenal or jejunal tissues in the ASA group compared to the control group. The stomach damage was less in melatonin treated groups, but the lesions were not completely eliminated. The jejunum in the ASA group retained a nearly normal appearance. We found that melatonin exhibited some healing effects on ASA induced duodenal mucosal injury.     

不同月龄大鼠空肠粘膜上皮细胞的形态、增殖及凋亡

为研究雄性大鼠空肠在发生、发育和衰老过程中上皮细胞增殖与凋亡形态学的变化,本实验采用增殖细胞核抗原(PCNA)免疫细胞化学染色、原位末端标记(TUNEL)法检测了不同生长发育阶段SD大鼠空肠绒毛粘膜上皮及小肠腺上皮的细胞增殖、凋亡的变化情况,并统计测量了不同发育阶段大鼠空肠绒毛的高度、肌层厚度及绒毛杯形细胞、肠腺杯形细胞的数量变化。观察到大鼠空肠肠腺隐窝增殖细胞的阳性着色表达从出生后开始增强,到3月龄时达最高峰,12月龄时增殖细胞阳性染色又减弱;凋亡细胞主要分布于固有层,凋亡阳性细胞数在3月龄最多;大鼠空肠绒毛的高度从初生后开始增加,到3月龄达顶峰,而后开始变矮;空肠肌层在3周龄、12月龄较厚;杯形细胞数量于生后3周迅速增长,不同发育阶段的大鼠空肠肠腺隐窝的杯形细胞数量与年龄呈正相关。     

Effect of cyclophosphamide on the proliferation of L 1210 ascites tumour cells and of jejunal crypt cells in the mouse

Cyclophosphamide (CY) does not act in a cell-cycle specific manner, i.e. exclusively on proliferating cells. It also kills non-proliferating cells, as shown by application of CY to L 1210 ascites tumour-bearing mice during plateau phase growth of the tumour. Moreover, treatment with CY of L 1210 ascites tumour cells, double-labelled with [3H] and [14C]-thymidine, suggests that CY is not cell cycle phase dependent, but kills cells out of all cycle phases. There is also an extensive cytocidal effect of CY (300 mg/kg) on the jejunal crypt cells of the mouse, which is even more pronounced than that of cisplatinum (DDP, 13 mg/kg). However, rapid regeneration of crypt cells occurs after treatment with the drugs.     

Effects of spaceflight, simulated spaceflight and countermeasures on single muscle fiber physiology

Since the first human flew in space in 1961, there has been extensive scientific interest in the responses of the human body and how it adapts to this unique environment. From the available data, it appears that all major systems in the human body undergo an adaptive change while in a microgravity environment. In particular the human muscle system appears to undergo loss of muscle mass and strength which greatly influences the maximal work capacity of the muscle. Recently, our research group has been involved in a series of whole muscle and cellular studies during periods of short duration space flight, bed rest, and unilateral lower limb suspension (ULLS) in an attempt to elucidate the changes that are occurring in the whole muscle and single muscle fiber contractile properties with unloading. In addition, various countermeasure activities for skeletal muscle have been part of the space flights and ground-based studies. The intention of this paper will be to briefly review our findings in whole muscle, cellular, and countermeasure effectiveness with human muscle.     

Effects of different phytosterol analogs on colonic mucosal cell proliferation in hamsters

OBJECTIVE: The aim of this study was to investigate the effects of different phytosterols and their analogs on colonic mucosal cell proliferation in hamsters. METHOD: Hamsters (n=70) were randomly assigned to seven groups after a 2-week acclimation and fed the experimental diet for 5 weeks. Diets included (i) the semipurified diet with no cholesterol (Con), (ii) the Con diet plus 0.25% cholesterol (Ch-con), or the Ch-con diet with (iii) 1% phytosterols (Ste), (iv) 1% phytostanols (Sta), (v) 1.76% sterol esters (esterified to fish oil, SteF), (vi) 0.71% stanol esters (esterified to ascorbic acid [disodium ascorbyl phytostanol phosphate, FM-VP4], 0.7% StaA) and (vii) 1.43% stanol esters (1.4% StaA), respectively. After 5 weeks on experimental diet, hamsters were sacrificed, and colons were collected. Colonic mucosal cell proliferation was measured by immunohistochemistry using monoclonal antibodies against antigen Ki-67. RESULTS: Colonic mucosal cell proliferation was 21.4% (P<.01) lower in the 0.7%, but not 1.4%, StaA relative to the Ch-con group. In addition, a lower (-13.9%) cell proliferation was observed in the SteF group in comparison to the Ch-con group; however, this difference achieved only a borderline level of statistical significance (P=.069). No differences were observed between Con and Ch-con, as well as among Ste, Sta, 1.4% StaA and Ch-con treatments. CONCLUSION: Plant stanols esterified to ascorbic acid may possess anticarcinogenic properties in the colon by suppressing colonic mucosa cell proliferation; however, this effect was not observed with free plant sterols or stanols.     

双歧杆菌对SD大鼠空肠黏膜分泌型免疫球蛋白A的影响

目的研究双歧杆菌的免疫佐剂效应。方法将SD大鼠随机分成3组,即卵清白蛋白（OVA）组,双歧杆菌＋OVA组和PBS空白对照组。各组给予免疫后,收集长约3cm的空肠,通过免疫组织化学技术和Qwin图像处理系统,对空肠分泌型免疫球蛋白A（sIgA）的定位进行系统分析,研究同时注射OVA和双歧杆菌后对SD大鼠在不同时期空肠中sIgA阳性细胞分泌的影响。结果在免疫后的SD大鼠的空肠内均产生了特异性的分泌型抗体sIgA,其中双歧杆菌＋OVA组显著高于其他2组（P〈0．05）。结论双歧杆菌经胃肠道黏膜免疫可诱导有效的免疫佐剂效应。     

Influence of the beta-adrenergic antagonists propranolol, practolol and oxprenolol on the proliferation of rat jejunal crypt cells

Beta-adrenergic blockade by quite large doses of propranolol, practolol and oxprenolol, once or continuously applied, does not influence jejunal crypt-cell proliferation in the rat. After a single i.p. injection of 20 mg/kg propranolol or practolol and even of 100 mg/kg practolol, the mitotic index, the labelling index and the duration of the S phase do not differ between treated and untreated control animals nor between animals treated with the different drugs. Continuous application of 30 mg/kg/d propranolol, practolol or oxprenolol for 7 or 14 days does not affect the mitotic and labelling indices either, nor does it change the duration of the cycle of the jejunal crypt cells and its phases as determined by the percent labelled mitoses method. These results are in contrast to those reported previously by Tutton & Helme (1974).     

胃缺血-再灌注对大鼠胃黏膜细胞凋亡和增殖的影响

本研究采用大鼠胃缺血-再灌注（gastricischemia-reperfusion,GI-R）模型（夹闭腹腔动脉30 min后再灌注）,通过组织学、免疫组化等方法,研究GI-R不同时间（0、0.5、1、3、6、24、48、72 h）对胃黏膜细胞凋亡和增殖的影响.结果发现,单纯缺血30 min胃黏膜损伤较轻,再灌注后损伤逐渐加重,胃黏膜的凋亡细胞迅速增加,而增殖细胞迅速减少;至再灌注后1 h达高峰;之后胃黏膜开始修复,凋亡细胞逐渐减少,增殖细胞逐渐增加;至再灌注后24 h胃黏膜细胞增殖达高峰;再灌注后72 h胃黏膜基本恢复正常.上述结果提示,在GI-R中,胃黏膜损伤主要由再灌注引起,凋亡细胞增加;然后胃黏膜启动自我修复机制,增殖细胞逐渐取代损伤细胞,3 d左右就可基本修复,表明胃黏膜细胞具有很强的自我修复能力.     

Effects of spaceflight on human calf hemodynamics.

Chronic microgravity may modify adaptations of the leg circulation to gravitational pressures. We measured resting calf compliance and blood flow with venous occlusion plethysmography, and arterial blood pressure with sphygmomanometry, in seven subjects before, during, and after spaceflight. Calf vascular resistance equaled mean arterial pressure divided by calf flow. Compliance equaled the slope of the calf volume change and venous occlusion pressure relationship for thigh cuff pressures of 20, 40, 60, and 80 mmHg held for 1, 2, 3, and 4 min, respectively, with 1-min breaks between occlusions. Calf blood flow decreased 41% in microgravity (to 1.15 +/- 0.16 ml x 100 ml(-1) x min(-1)) relative to 1-G supine conditions (1.94 +/- 0.19 ml x 100 ml(-1) x min(-1), P = 0.01), and arterial pressure tended to increase (P = 0.05), such that calf vascular resistance doubled in microgravity (preflight: 43 +/- 4 units; in-flight: 83 +/- 13 units; P < 0.001) yet returned to preflight levels after flight. Calf compliance remained unchanged in microgravity but tended to increase during the first week postflight (P > 0.2). Calf vasoconstriction in microgravity qualitatively agrees with the "upright set-point" hypothesis: the circulation seeks conditions approximating upright posture on Earth. No calf hemodynamic result exhibited obvious mechanistic implications for postflight orthostatic intolerance.     

Re-examination of the effect of beta-adrenergic blocking agents on the proliferation of rat jejunal crypt cells using the stathmokinetic method

Reports of the effects of beta-adrenergic receptor blocking agents on the proliferative activity of rat jejunal crypt cells are contradictory. According to Tutton and Helme (1974) a single injection of propranolol or practolol (10 mg/kg) increased the mitotic index twofold and shortened the duration of the cell cycle of the crypt cells. However, upon repeating the experiments with double the dose of propranolol, Maurer-Schultze et al. (1986) observed no such effects using cell kinetic methods with 3H-thymidine instead of the stathmokinetic method applied by Tutton and Helme. Since the discrepancy in the results may have been due to methodological differences the same stathmokinetic method used by Tutton and Helme has been applied in the present work. However, the results obtained with this method indicate no influence by propranolol on the proliferation of jejunal crypt cells even with a dose of 20 mg/kg. Consequently we were unable to confirm the stimulant effect of propranolol on crypt cell proliferation. The possible causes of the discrepancy between the present results and those of Tutton and Helme are discussed.     

氧化苦参碱对K562肿瘤细胞增殖的影响

目的:研究氧化苦参碱(OM)对人白血痛细胞系K562生长增殖的影响.方法:运用MTT比色法、活细胞计数法、集落形成法以及透射电镜观察检测OM对人白血病细胞系K562增殖抑制作用.结果:MTT实验、生长曲线及集落形成实验显示OM能明显抑制K562细胞的增殖.随着OM浓度的增加,K562细胞存活细胞显著降低,呈现明显的刺量依赖性,经相关分析,细胞抑制率与OM浓度呈正相关(r=0.9010),其半数抑制浓度(IC50)为0.33 mg/ml.透射电镜下显示在低浓度即有明显的诱导细胞凋亡的作用,出现核固缩、核碎裂、凋亡小体等典型的凋亡形态.结论:OM具有抑制K562白血病细胞增殖诱导肿瘤细胞凋亡的作用.     

低氧对胚胎干细胞增殖的影响

目的:观察间歇性低氧和持续性低氧对体外培养的胚胎干细胞(ES细胞)增殖的影响.方法:利用细胞记数法和BrdU (5-溴脱氧尿苷)掺入的流式细胞分析检测细胞增殖,并用RT -PCR的方法检测低氧诱导因子(HIF-1a)的表达变化.结果:①将ES细胞分别放在低氧(3%～10% O2)和常氧(20% O2)的环境中培养24 h后,在低氧环境中培养的ES细胞数较常氧组明显减少;②将ES细胞分别给予间歇性低氧刺激(3%～10% O2),每天10 min,连续4 d后,发现3%低氧组较常氧对照组的细胞增殖明显升高.③用RT-PCR方法观察HIF-1a的表达与细胞增殖的关系,发现在常氧环境中培养的ES即有HIF-1a的表达,ES细胞在持续低氧24 h或间歇性低氧(3%～10% O2)刺激4 d后对HIF-1a的表达均无明显影响.结论:间歇性低氧(3% O2)可明显促进体外培养的ES细胞增殖,而持续性低氧抑制ES细胞增殖,间歇性低氧(3% O2)刺激促进ES细胞增殖的机制尚有待于进一步的研究.