Human mesangial cells synthesize interleukin 1 alpha but not interleukin 1 beta, interleukin 1 receptor antagonist, or tumour necrosis factor.

There is controversy over whether mesangial cells synthesize and release IL-1 and TNF, and many of the positive experiments were performed before specific reagents and molecular probes were available. Consequently we have stimulated human mesangial cells using protocols known to stimulate the synthesis of other cytokines. No mRNA for IL-1 beta or TNF could be detected in quiescent or proliferating mesangial cells irrespective of whether they had been exposed to cytokines or not. In contrast mRNA for IL-1 alpha was detected in cells stimulated with IL-1 beta 10 ng/ml or with TNF 500 ng/ml; IL-1 alpha was also detected in cell lysates from stimulated mesangial cells. We could not detect mRNA for IL-1 receptor antagonist in any of the cell preparations. These results suggest that mesangial cells are unlikely to be a major source of IL-1 beta or TNF.     

The effect of interleukin 1 alpha on survival in a murine model of burn wound sepsis

We examined the effects of human recombinant interleukin 1 alpha (IL-1 alpha) in a murine model of burn wound sepsis. The BDF1 male mice received a 15% burn injury, followed by burn wound inoculation with Pseudomonas aeruginosa. Improvement in survival was noted in the mice that received a single injection of 100 or 1000 ng of IL-1 alpha in comparison with the control animals (IL-1 alpha, 100 ng vs control, 60% vs 13%; IL-1 alpha, 1000 ng vs control, 40% vs 0%). The animals that received 1 ng twice daily for 7 days had improved survival in comparison with the controls (IL-1 alpha vs control, 70.8% vs 20.8%). The animals that received a single injection of 1000 ng after a bacterial challenge with 10(4) P aeruginosa of IL-1 alpha had fewer positive blood cultures at 48 hours compared with the controls (57% vs 89%). In addition, the animals that received 100 ng of IL-1 alpha had significantly increased absolute neutrophil counts at 6, 24, and 48 hours after thermal injury and bacterial challenge with 10(3) colony-forming units of P aeruginosa. The use of cytokines to modulate the host response to injury or infection may lead to additional strategies to improve the outcome following burn injury.     

Synthesis of acute-phase proteins in perfused liver following administration of recombinant interleukin 1 alpha to normal or adrenalectomized rats

The purpose of this study was to investigate the effects of recombinant interleukin 1 alpha (rIL-1 alpha) on metabolic rate and synthesis of acute-phase proteins in intact and adrenalectomized rats. Animals were housed in metabolic cages with daily recording of food intake and body weight. Twice daily, for 3 days, the rats were injected intraperitoneally with 5000 LAF U of human rIL-1 alpha, purified from Escherichia coli. Control animals were pair-fed and received corresponding injections with saline. In the morning of the fourth day, resting energy expenditure (REE) was determined by indirect calorimetry, and synthesis of total secreted proteins, albumin, complement component C3, and seromucoid fraction was measured by radioimmunological method using rat-specific antisera and [3H]leucine in livers perfused for 2 hr. Food intake decreased by approximately 30% during rIL-1 alpha administration to intact rats. The decrease in food intake occurred later and was less pronounced in adrenalectomized rats receiving rIL-1 alpha. Growth rate was significantly reduced on the first day of rIL-1 alpha treatment in intact rats, while there was no effect on growth rate in adrenalectomized animals. After rIL-1 alpha administration, REE was increased by 26% in intact rats (P less than 0.001) and by 14% in adrenalectomized rats (N.S.). Increased synthesis rates of total secreted proteins, complement component C3, and seromucoid fraction were observed in livers of intact rats following rIL-1 alpha administration. In adrenalectomized rats, only production of C3 was significantly increased after treatment with rIL-1 alpha. Albumin synthesis rate was not changed in either group following rIL-1 alpha injections.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fate of swallowed interleukin 8 and TNF alpha, and effect on the Wistar rat gut.

To evaluate the passage of cytokines through the gastrointestinal tract, we investigated the digestion of interleukin-8 (IL-8) and tumour necrosis factor alpha (TNF alpha), in vitro and in vivo, and their propensity to induce intestinal inflammation. We serially immuno-assayed IL-8 and TNF alpha solutions co-incubated with each of three pancreatin preparations at pH 4.5 and pH 8. We gavaged IL-8, TNF alpha and marker into 15 Wistar rats, and measured their faecal cytokine concentrations by ELISA and histologically examined their guts. IL-8 immunoreactivity was extinguished by all pancreatin preparations after 1 h of incubation at 37 degrees C. TNF alpha concentration progressively fell from 1 to 4 h with all enzyme preparations. Buffer control samples maintained their cytokine concentrations throughout incubation. No IL-8 or TNF alpha was detected in any rat faecal pellets. There was no significant proinflammatory effect of the gavaged cytokines on rat intestine. IL-8 and TNF alpha in aqueous solution could well be fully digested in the CF gut when transit time is normal and exogenous enzymes are provided, although cytokines swallowed in viscous sputum may be protected from such digestion.     

Macrophage inflammatory protein-1alpha induces hypercalcemia in adult T-cell leukemia.

Hypercalcemia is observed in >80% of ATL. Serum MIP-1alpha levels were elevated in all 24 ATL with hypercalcemia but undetectable in all 10 patients with humoral hypercalcemia of malignancy with solid tumors and in 34 of 37 ATL without hypercalcemia. We propose that serum MIP-1alpha is a clinical hallmark for hypercalcemia in ATL. INTRODUCTION: High serum cytokines levels are not always associated with hypercalcemia in patients with adult T-cell leukemia (ATL), suggesting that other factors are involved in the pathogenesis of ATL patients with hypercalcemia. This study was designed to determine the role of macrophage inflammatory protein-1alpha (MIP-1alpha), a chemokine recently described as an osteoclast stimulatory factor, in ATL-associated hypercalcemia. MATERIALS AND METHODS: We measured serum interleukin (IL)-1beta, IL-6, TNF-alpha, parathyroid hormone-related protein (PTHrP), and MIP-1alpha levels in ATL patients by enzyme-linked immunosorbent assays. FACScan was used to measure the expression of RANKL on ATL cells. Osteoclast formation in cocultures of ATL cells and peripheral blood mononuclear cells (PBMCs) was evaluated by TRACP staining. RESULTS: High serum MIP-1alpha levels were noted in all 24 ATL patients with hypercalcemia and in 3 of 37 ATL patients without hypercalcemia. The elevated levels of MIP-1alpha and calcium in ATL patients decreased after effective chemotherapy, emphasizing the role of MIP-1alpha in ATL hypercalcemia. ATL cells spontaneously produced MIP-1alpha. MIP-1alpha significantly enhanced human monocyte (precursor cells of osteoclasts) migration and induced RANKL expression on ATL cells. ATL cell-induced osteoclast formation from PBMCs was inhibited by anti-MIP-1alpha antibody and osteoprotegerin. CONCLUSION: Our results suggest that MIP-1alpha can induce RANKL on ATL cells in autocrine fashion and that RANKL seems to mediate the hypercalcemic effect of MIP-1alpha in ATL. We propose that MIP-1alpha is the clinical hallmark of hypercalcemia in ATL and could be a potentially useful therapeutic target.     

alpha1-Adrenoceptors during simulated ischemia and reoxygenation of the human myocardium: effect of the dose and time of administration.

OBJECTIVE: We sought to investigate the effect of alpha1-adrenoceptor activity on the ischemic and reoxygenated human myocardium. METHODS: Right atrial appendages (n = 6 per group) obtained during elective cardiac operations were sliced and stabilized in normoxic normothermic buffer solution for 30 minutes and then subjected to 90 minutes of simulated ischemia, followed by 120 minutes of reoxygenation. In study 1 the dose responses to the alpha1-adrenoceptor agonist phenylephrine (0.01, 0.1, 1, 10, and 100 micromol/L) and to the alpha1-adrenoceptor antagonist prazosin (0.1, 1, 10, and 100 micromol/L) when administered for 10 minutes before ischemia, during ischemia, and during reoxygenation were examined. The influence of the time of administration (ie, before ischemia, during ischemia, or during reoxygenation) of phenylephrine (0.1 micromol/L) and prazosin (10 micromol/L) was then investigated in study 2. In study 3 the effect of the combined administration of phenylephrine given before ischemia and prazosin given during ischemia was investigated. In study 4 the protective effect of phenylephrine given before ischemia (for 10 minutes or for 5 minutes with a 5-minute washout period) was compared with that of ischemic preconditioning (5 minutes of ischemia and 5 minutes of reoxygenation). At the end of each protocol, the leakage of creatine kinase (in units per gram of wet weight) and the reduction of 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide to insoluble formazan dye (in millimoles per gram of wet weight) were measured. RESULTS: Phenylephrine is maximally beneficial at 0.1 and 1 micromol/L (creatinine kinase, 0.97 +/- 0.06 and 0.95 +/- 0.03 U/g, respectively; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 153.0 +/- 7.8 and 156.2 +/- 6.7 mmol/g, respectively) compared with ischemic control (creatine kinase, 1.87 +/- 0.03 U/g; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 108.5 +/- 6.8 mmol/g; P <.05) but prazosin is detrimental at concentrations above 10 micromol/L (creatine kinase, 5.22 +/- 0.29 U/g; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 69.8 +/- 2.9 mmol/g; P <.05 vs ischemic control). In addition, phenylephrine (0.1 micromol/L) is protective when given before ischemia (creatine kinase, 2.06 +/- 0.21 U/g; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 148.5 +/- 4.5 mmol/g; P <.05 vs ischemic control) but is detrimental when given during ischemia alone (creatine kinase, 4.49 +/- 0.98 U/g; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 70.5 +/- 6.1 mmol/g; P <.05 vs ischemic control) and has no significant effect during reoxygenation. In contrast, prazosin (10 micromol/L) is beneficial when given during ischemia alone (creatine kinase, 1.34 +/- 0.10 U/g; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 148.5 +/- 4.5 mmol/g; P <.05 vs ischemic control), is detrimental when given during reoxygenation alone (creatine kinase, 1.5 +/- 0.16 U/g; 3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, 85.0 +/- 4.7 mmol/g; P <.05 vs ischemic control), and has no effect when given before ischemia. The use of phenylephrine before ischemia alone is as protective as prazosin given during ischemia alone, but the combination of the two drugs does not cause additional benefit. Interestingly, the protection afforded by phenylephrine when given before ischemia is similar to that obtained with ischemic preconditioning. CONCLUSIONS: In the human myocardium activation of alpha1-adrenoceptors before ischemia is protective but is detrimental during ischemia, whereas blockade of alpha1-adrenoceptors is beneficial during ischemia but detrimental during reoxygenation. The degree of protection achieved by activation of the alpha1-adrenoceptors before ischemia is similar to that obtained with blockade of alpha1-adrenoceptors during ischemia and that of ischemic preconditioning.     

表达趋化因子MIP-1α的小鼠肝癌疫苗抗肿瘤活性的研究

目的　探讨小鼠趋化因子 (mMIP 1α)的重组腺病毒载体 (AdmMIP 1α)体外感染肝癌细胞株Hepa1 6后 ,其体内抗肿瘤活性及其成为肝癌疫苗的可能性。　方法　腺病毒载体体外感染Hepa1 6细胞 ,通过绿色荧光蛋白 (GFP)的表达检测感染效率 ;每天细胞计数 (连续 14d)观察细胞的体外生长曲线 ;取 5× 10 6个修饰后的Hepa1 6细胞接种C5 7BL/ 6小鼠 ,4周后在AdmMIP 1α组未荷瘤小鼠原接种部位的对侧再接种 2× 10 6个野生型Hepa1 6或EL4细胞 ,观察肿瘤大小并作统计学处理。结果　AdmMIP 1α能有效感染靶细胞Hepa1 6 ,感染前、后Hepa1 6的体外生长无明显改变 ;修饰后Hepa1 6细胞的体内成瘤性下降 ;4周后再接种Hepa1 6细胞 ,肿瘤生长速度显著降低 ;而再接种的EL4细胞呈渐进性生长 ,与对照组差异无显著意义。　结论　表达mMIP 1α基因的肝癌细胞的体内成瘤性下降 ,能激发特异性免疫保护反应 ,有可能成为有效的肝癌疫苗。     

The effect of pre-operative administration of midazolam on the development of intra-operative hypothermia

(Midazolam is often used for premedication; it is known to promote vasodilation and may therefore affect redistribution of heat during surgery. We examined the effect of pre-operative administration of midazolam on the development of intra-operative hypothermia. Forty-five patients were randomly allocated to one of three groups to receive no premedication (Group C), IM midazolam 0.04 mg.kg(-1) (Group M1) or 0.08 mg.kg(-1) (Group M2) 30 min prior to anaesthesia. Sedation levels were assessed, and then general anaesthesia was induced and maintained using propofol and fentanyl. During surgery, core temperature, which was similar for the three groups prior to induction of anaesthesia, decreased significantly less in the midazolam groups M1 and M2 compared to the control group C. Patients who were more heavily sedated prior to induction of anaesthesia, had significantly lower core temperatures peri-operatively than those who were less sedated, and core temperatures in unpremedicated patients fell to significantly lower levels during surgery than those who were drowsy. We conclude that pre-operative administration of midazolam produces an effect on the development of peri-operative hypothermia. We found that moderate pre-operative sedation reduces the peri-operative heat loss, possibly by affecting core-to-peripheral heat distribution.     

Effect of calcitriol on the secretion of prostaglandin E2, interleukin 1, and tumor necrosis factor alpha by human monocytes.

Cells of the monocyte/macrophage lineage express specific receptors for calcitriol (1,25-dihydroxyvitamin D3) and secrete prostaglandins and several cytokines with potent effects on bone metabolism. The aim of this study was to determine the effect of calcitriol on the secretion of prostaglandin E2 (PGE2), interleukin-1 (IL-1), and tumor necrosis factor (TNF alpha). Monocyte-enriched peripheral blood mononuclear cells (PBMC) from healthy subjects were cultured in the presence or absence of calcitriol (10(-11)-10(-7) M) and several stimulating agents. After 24 h, PGE2, IL-1, and TNF alpha were measured in the culture supernatants or lysates with specific immunoassays. Calcitriol induced a biphasic effect on PGE2 production by unstimulated cells and increased PGE2 synthesis by cells stimulated with either endotoxin or tau-interferon (IFN-tau). On the other hand, calcitriol inhibited the production of TNF alpha by monocytes stimulated with either IFN-tau or phorbol esters. This effect was not prevented by the addition of indomethacin, IL-1, or IL-2. Under the conditions used, we observed no effect of calcitriol on IL-1 alpha or IL-1 beta production. These results indicate that calcitriol induces in vitro marked changes in the secretion of monocyte products with known activity on bone cells. Further studies are needed to elucidate whether some effects of calcitriol on bone metabolism are mediated by the interaction of the sterol with cells of the immune system.     

Role of urinary alpha1-globulin fraction in formation of urinary calculi. With special reference to aggregating effect of serum alpha1-globulin on calcium carbonate suspension.

The present study was undertaken to determine if urinary protein can produce urinary stones and what types of protein have such an effect. Normal human serum was fractionated first with ammonium sulfate and then with DEAE-cellulose. The stone-forming action of each fraction was estimated by calculating their ability to alter the sedimentation rate and zeta-potential of a calcium carbonate suspension. Finally, the proteins in each fraction were identified by cellulose acetate electrophoresis. The most marked aggregating and precipitating effect on a CaCO3 suspension was observed with a mixture of proteins of alpha1-globulin and albumin fractions. However, beta- and gamma-fractions had little aggregating effect on the CaCO3 suspension.     

Ganglioside GM1 deficiency in effector T cells from NOD mice induces resistance to regulatory T-cell suppression

OBJECTIVE

To detect GM1 deficiency and determine its role in effector T cells (Teffs) from NOD mice in establishing resistance to regulatory T-cell (Treg) suppression.

RESEARCH DESIGN AND METHODS

CD4⁺ and CD8⁺ Teffs were isolated from spleens of prediabetic NOD mice for comparison with similar cells from Balb/c, C57BL/6, and NOR mice. GM1 was quantified with thin-layer chromatography for total cellular GM1 and flow cytometry for cell-surface GM1. Suppression of Teff proliferation was determined by application of GM1 cross-linking agents or coculturing with Tregs. Calcium influx in Teffs was quantified using fura-2.

RESULTS

Resting and activated CD4⁺ and CD8⁺ Teffs of NOD mice contained significantly less GM1 than Teffs from the other three mouse strains tested. After activation, NOD Teffs resisted suppression by Tregs or GM1 cross-linking agents in contrast to robust suppression of Balb/c Teffs; this was reversed by preincubation of NOD Teffs with GM1. NOD Teffs also showed attenuated Ca²⁺ influx via transient receptor potential channel 5 (TRPC5) channels induced by GM1 cross-linking, and this, too, was reversed by elevation of Teff GM1.

CONCLUSIONS

GM1 deficiency occurs in NOD Teffs and contributes importantly to failed suppression, which is rectified by increasing Teff GM1. Such elevation also reverses subthreshold Ca²⁺ influx via TRPC5 channels, an essential aspect of suppression. Our results also support a critical role for galectin-1 as a GM1 cross-linking counter-receptor that fittingly is upregulated and released by Tregs during activation. These findings suggest a novel mechanism by which pathogenic Teffs evade regulatory suppression, thereby leading to autoimmune β-cell destruction and type 1 diabetes.Pancreatic β-cell destruction in type 1 diabetes is the net effect of antigen-specific effector T cells (Teffs) evading the protective defense of regulatory T cells (Tregs) (1,2). The homeostatic balance between Teffs and Tregs is critically important in maintaining control over “rogue” effector responses that lead to autoimmune disease (2). Studies in NOD mice have identified defects in both Teff and Treg populations that contribute to immune islet damage. However, recent work has demonstrated that Tregs purified from NOD and Balb/c mice are capable of suppressing the proliferative response of Teffs obtained from Balb/c mice, but not from NOD mice (3). Similar findings have been demonstrated in human subjects with type 1 diabetes compared with nondiabetic control subjects and subjects with type 2 diabetes (4). These studies suggest that NOD mice and human subjects with type 1 diabetes both harbor a primary defect in Teffs that confers resistance to Treg suppression. This as yet biochemically undefined functional defect in Teffs is likely to play an important role in the pathogenesis of type 1 diabetes. This study was designed to test the hypothesis of deficient functional interplay between the protein effector, galectin-1 (Gal-1), and its ganglioside counter-receptor, GM1.Ganglioside GM1 is an integral component of lipid raft microdomains with numerous functions, including regulation of Ca²⁺ channel activity and coincident downstream signaling (5,6). Of particular note in this context is the robust upregulation of GM1 in Teffs during polyclonal activation that promotes more extensive cross-linking of cell-surface GM1 by homodimeric Gal-1, a protein secreted by Tregs; such interaction was previously shown to activate transient receptor potential channel 5 (TRPC5) Ca²⁺ channels and suppress further Teff proliferation (7). This interaction between GM1 on Teffs and secreted Gal-1 from Tregs is one mechanism by which Tregs apparently can maintain homeostatic control over “rogue” Teff populations. The observation that the cholera toxin B (CtxB) subunit, a multivalent counter-receptor that binds with high affinity and specificity to GM1 (8), produced the same effects as the Treg product Gal-1 served to emphasize the pivotal role of GM1 cross-linking in Teff suppression (7). Thus, GM1 could function as a molecular switch in Teff homeostasis.In the current study, we identify for the first time a fundamental deficiency of cell-surface GM1 in CD4⁺ and CD8⁺ Teffs from NOD mice that we propose underlies their resistance to Treg suppression. NOD Teffs are shown to resist TRPC5-mediated Ca²⁺ influx and proliferation suppression when treated with Gal-1 or CtxB. Pretreatment of NOD Teffs with GM1 enhanced Ca²⁺ influx and restored Teff suppression by both Tregs and the two previously mentioned GM1 cross-linking agents. Significantly, anti–Gal-1 antibody (Ab) blocked Balb/c Treg suppression of Teffs, pointing to Gal-1 as key effector in this form of intercellular communication. These results are consonant with NOD mouse studies in which type 1 diabetes was prevented by Gal-1 (9) and delayed with reduced frequency by GM1 (10). This action of Gal-1 parallels that previously reported for CtxB in preventing diabetes in the NOD mouse (11). Our findings suggest a novel mechanism by which pathogenic Teffs escape regulatory suppression, thereby leading to autoimmune β-cell destruction and type 1 diabetes.     

Successful combination immunotherapy for the generation in vivo of antitumor activity with anti-CD3, interleukin 2, and tumor necrosis factor alpha

The purpose of this study was to generate lymphokine-activated killer cells via alternative pathways using combinations of biologic agents. Immunotherapy with the mouse anti-CD3 analogue combined with low-dose interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-alpha) was tested for in vivo antitumor efficacy against established pulmonary metastases from a variety of mouse tumor-cell lines. Administration of a single dose of anti-CD3 followed by low-dose IL-2 and TNF-alpha potentiated reduction of metastases compared with higher doses of IL-2 alone or IL-2 plus TNF-alpha. Treatment with anti-CD3 plus IL-2 plus TNF-alpha significantly prolonged survival and resulted in 60% of the mice achieving long-term survival compared with no survival using single agents or other combinations. The lymphokine-activated killer and natural killer activities of mouse splenocytes increased following treatment with anti-CD3 plus IL-2 plus TNF-alpha. These results indicate that the sequential use of anti-CD3, IL-2, and TNF-alpha for the induction and maintenance of lymphokine-activated killer activity potentiates antitumor activity and provides novel strategies for combination immunotherapy.     

Decreased interleukin generation in patients with cancer of the digestive system. A correlation between interleukin 1 and interleukin 2 production

The generating capacity of interleukin 1 (IL-1) and interleukin 2 (IL-2) by peripheral blood mononuclear cells (PBMNC) was measured in 40 patients with digestive cancer (20 localized and 20 disseminated) and 20 age- and sex-matched control subjects. The localized carcinoma patients showed normal IL-1 production and a significantly depressed IL-2 production (p less than 0.05) when compared to the healthy individuals. The disseminated carcinoma patients exhibited a significant impairment of both IL-1 and IL-2 production in comparison with the healthy controls (IL-1: p less than 0.001, IL-2: p less than 0.001) and the localized carcinoma patients (IL-1: p less than 0.001, IL-2: p less than 0.001). A significant correlation was observed between IL-1 and IL-2 generation in all the cancer patients (r = 0.458, p less than 0.01). These results suggest that progressive tumor growth may result in decreased interleukin production by the host PBMNC, and that related mechanisms, which are more susceptible to lymphocytes than monocytes, may be involved in the impairment of both IL-1 and IL-2 production.     

甲基莲心碱增强阿霉素抑制骨肉瘤作用

目的探讨甲基莲心碱增强阿霉素抑制裸鼠体内骨肉瘤生长的作用。方法将人成骨瘤细胞(MG-63)接种于BALB／C裸鼠,建立人成骨肉瘤裸鼠移植模型。随机分4组:生理盐水组 (Ns)、甲基莲心碱组(Nef)、阿霉素组(Adr)、甲基莲心碱+阿霉素组(Nef+Adr)。腹腔内注射以上药物,Nef浓度3．0mg／kg体重、Adr 2．0mg／kg体重。测量瘤重、计算瘤重抑制率、制病理切片,在光镜下观察肿瘤形态与改变。流式细胞术检测肿瘤原发灶细胞凋亡。结果 Ns、Nef、ADR、Nef+ ADR组原发肿瘤重量分别为:(8．03±0．92)、(7．86±0．80)、(4．16±0．54)、(1．86±0．73)g,Nef+ ADR组肿瘤重量较ADR组显著减轻(P<0．05);Nef、ADR合并用药效果α=1．38。4组原发灶细胞凋亡率分别为8．29％、11．80％、25．70％、71．20％,Nef+ADR组较ADR组明显增高(P<0．05)。病理切片发现Nef+ADR组较ADR组肿瘤细胞明显减少,坏死明显增多。结论甲基莲心碱对阿霉素抑制裸鼠体内骨肉瘤生长有增效作用。