氨基胍对骨关节炎软骨细胞诱导型一氧化氮合酶的影响

目的:研究氨基胍对骨关节炎软骨细胞诱导型一氧化氮合酶的影响。方法:将32只兔子随机分组,正常组不予任何处理,试验组及对照组行右后肢伸直位管型石膏固定造模,试验组腹腔内注射氨基胍硫酸盐溶液100mg/(kg·d),对照组每天腹腔内注射相同体积的生理盐水。分别于4周和8周处死动物,切取标本进行后续研究。结果:与对照组相比,试验组在大体形态、HE染色方面更接近于正常组、iNOS表达阳性细胞数较少。结论:氨基胍能有效减少iNOS表达,延缓骨性关节炎的病情发展。

Protective effect of inducible nitric oxide synthase inhibitor on pancreas transplantation in rats

AIM: To investigate the effect of inducible nitric oxide synthase inhibitor, aminoguanidine, on pancreas transplantation in rats. METHODS: A model of pancreas transplantation was established in rats. Streptozotocin-induced diabetic male Wistar rats were randomly assigned to sham-operation control group (n= 6), transplant control group (n= 6), and aminoguanidine (AG) treatment group (n=18). In the AG group, aminoguanidine was added to intravascular infusion as the onset of reperfusion at the dose of 60 mg/kg, 80 mg/kg, 100 mg/kg body weight, respectively. Serum nitric oxide (NO) level, blood sugar and amylase activity were detected. Nitric oxide synthase (NOS) test kit was used to detect the pancreas cNOS and inducible NOS (iNOS) activity. Pancreas sections stained with HE and immunohistochemistry were evaluated under a light microscope. RESULTS: As compared with the transplant control group, the serum NO level and amylase activity decreased obviously and the evidence for pancreas injury was much less in the AG group. The AG (80 mg/kg body weight) group showed the most signifi cant difference in NO and amylase (NO: 66.0 ± 16.6 vs 192.3 ± 60.0, P < 0.01 and amylase: 1426 ± 177 vs 4477 ± 630, P < 0.01). The expression and activity of tissue iNOS, and blood sugar in the AG (80 mg/kg body weight) group were much lower than those in the transplant control group (iNOS: 2.01 ± 0.23 vs 26.59 ± 5.78, P < 0.01 and blood sugar: 14.2 ± 0.9 vs 16.8 ± 1.1, P < 0.01). CONCLUSION: Selective iNOS inhibitor, aminoguanidine as a free radical, has a protective effect on pancreas transplantation in rats by inhibiting NO and reducing its toxicity.

Aminoguanidine impedes human pancreatic tumor growth and metastasis development in nude mice

AIM:To study the action of aminoguanidine on pancreatic cancer xenografts in relation to cell proliferation,apoptosis,redox status and vascularization.METHODS:Xenografts of PANC-1 cells were developed in nude mice. The animals were separated into two groups:control and aminoguanidine treated. Tumor growth,survival and appearance of metastases were determined in vivo in both groups. Tumors were excised and ex vivo histochemical studies were performed. Cell growth was assessed by Ki-67 expression. Apoptosis was studied by intratumoral expression of B cell lymphoma-2 protein (Bcl-2) family proteins and Terminal deoxynucleotidyl transferase biotin-dUTP Nick End Labeling (Tunel). Redox status was evaluated by the expression of endothelial nitric oxide synthase (eNOS),catalase,copper-zinc superoxide dismutase (CuZnSOD),manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPx). Finally,vascularization was determined by Massons trichromic staining,and by VEGF and CD34 expression.RESULTS:Tumor volumes after 32 d of treatment by aminoguanidine (AG) were significantly lower than in control mice (P < 0.01). Median survival of AG mice was significantly greater than control animals (P < 0.01). The appearance of both homolateral and contralateral palpable metastases was significantly delayed in AG group. Apoptotic cells,intratumoral vascularization (trichromic stain) and the expression of Ki-67,Bax,eNOS,CD34,VEGF,catalase,CuZnSOD and MnSOD were diminished in AG treated mice (P < 0.01),while the expression of Bcl-2 and GPx did not change.CONCLUSION:The antitumoral action of aminoguanidine is associated with decreased cell proliferation,reduced angiogenesis,and reduced expression of antioxidant enzymes.

Effect of Temperature on Volumetric and Viscometric Properties of Homologous Amino Acids in Aqueous Solutions of Metformin Hydrochloride

Density（ρ）and viscosity（η）are measured for glycine,DL-α-alanine DL-α-valine,and DL-α-leucine in 0.05,0.10,0.15 and 0.20 mol·L^-1aqueous metformin hydrochloride at 308.15,313.15 and 318.15 K.The measured values are used to estimate some important parameters,such as partial molal volume Vφ,standard partial molal volume Vφ^0,transfer volume ΔVφ^0,hydration number nH,the second derivative of infinite dilution of partial molal volume with respect to temperature,viz., ^2 Vφ^0 /T^2,viscosity B-coefficient,variation of B with temperature,viz., dB/dT,free energy of activation per mole of solvent Δμ1^＊0 and solute Δμ2^0＊ of the amino acids.These parameters are interpreted in terms of solute-solute and solute-solvent interactions and structure making/breaking ability of solutes in the given solution.In addition,Vφ^0,0 ΔVφ^0,viscosity B-coefficient,ΔB and Δμ2 ^0＊ are split into group contributions（NH3^＋ COO ^-）and -CH2 of the amino acids using their linear correlation and their behavior is discussed.

Synthesis of a series of guanidine substituted derivatives of aminoglycosides

A novel method to prepare guanidine substituted aminoglycoside derivatives was developed.Free guanidine reacted with Cbz-protected aminoglycosides to produce guanidinylcarbonyl substituted derivatives.A methoxycarbonyl-protected intermediate was isolated,and the mechanism of guanidinylcarbonyl modification was proposed.With this method,six per- or part-guanidylcarbonyl substituted aminoglycosides were successfully obtained in good yields.Their in vitro antibacterial activities were essayed.