Preparation and evaluation of RGD and TAT co-modified paclitaxel loaded liposome / 中南大学学报(医学版)

OBJECTIVE@#To prepare Arg-Gly-Asp (RGD) and cell penetrating peptide TAT co-modified paclitaxel loaded liposome (RGD/TAT-LP-PTX) for MCF-7 cell inhibition.@*METHODS@#The co-modified liposome was prepared by film-ultrasonic method. The appearance, particle size and zeta potential were evaluated. The cellular uptake by MCF-7 cells in vitro was used to evaluate the targeting efficiency. The anti-proliferation efficiency of RGD/TAT-LP-PTX was evaluated by MTT assay. Tumor spheroids were used to evaluate anti-tumor ability of RGD/TAT-LP-PTX in vitro.@*RESULTS@#The particle diameter of the co-modified liposome was (138.8 ± 12.4) nm with the Zeta potential of (25.85 ± 2.75) mV. The entrapment efficiency of PTX was 88.3%. The RGD/TAT-LP uptaken by MCF-7 cells at 4 h was 1.79 times higher than that at 2 h. The co-modified liposome uptaken by MCF-7 cells was 2.25 and 2.72 times higher than that of TAT-LP and RGD-LP, respectively. The anti-proliferation rate of RGD/TAT-LP-PTX increased with time. The inhibition rate of RGD/TAT-LP-PTX for MCF-7 cells at 48 h was 1.78 times higher than that at 24 h. The MTT assay demonstrated the cell viability of RGD/TAT-LP-PTX was 1.65, 1.82 and 2.55 times higher than that of TAT-LP-PTX, RGD-LP-PTX and LP-PTX, respectively.@*CONCLUSION@#Co-modified liposome may serve as a promising breast cancer delivery system for antitumor drugs.

Effects of rosiglitazone on interlukin-6 and interlukin-10 levels in lung tissue of diabetic rats / 中国综合临床

Objective To observe the effect of rosiglitazone on the concentration of interlukin (IL)-6 and IL-10 in lung tissues of diabetic rats.Methods The experimental diabetic rats were yielded by injecting streptozotocin(STZ) and feeding with high fat and high glucose food.We observed lung morphology in control group,diabetes mellitus(DM) group,and rosiglitazone group at 10 week and 20 week respectively under light microscope.Alteration of IL-6 and IL-10 in lung was measured by immunohistochemistry.Results The optical density values of IL-6 in the control group,the DM group and the roggerosiglitazone treatment group were 0.15 ±0.01,0.16 ±0.01;0.22 ±0.02,0.31 ±0.04;0.22 ±0.03,and 0.20 ±0.02 at 10 week and 20 week respectively (Fwithin =216.89,P ＜ 0.01 ; Fbetween =342.62,P ＜ 0.01 ; Finteraction =341.51,P ＜ 0.01).Any two groups had significant difference(P ＜ 0.05) except the comparison of the IL-6 values at 10 week and 20 week in the control group (P ＞ 0.05).The absorbance values of IL-10 in the three groups were 0.13 ± 0.01,0.15 ±0.02;0.20 ±0.01,0.21 ±0.01;0.20 ±0.02,and 0.17 ±0.01 at 10 week and 20 week respectively (Fwithin =14.612,P ＜0.01 ;Fbetween =909.19,P ＜0.01 ;Finteraction =210.55,P ＜0.01).Any two groups had significant difference(P ＜0.05) except the comparison of the IL-6 values at 10 week and 20 week in the control group.Conclusion The elevated levels of IL-6 and IL-10 in lung tissue of dibtetic rats might be related to the inflammation of lung tissues.Rosiglitazone may alleviate lung inflammation by regulating the levels of IL-6 and IL-10.

Changes of expression of signaling pathway of NF-κB/IκB in rat lung tissue with diabetes / 中国综合临床

Objective To investigate the effect of activation of NF-κB signaling pathway on pathogenesis of lung in diabetes mellitus(DM) rat. Methods The experimental type 2 diabetic rats were built by injecting streptozotocin (STZ) and feeding with high fat and glucose food. At the 12nd and 24th week, we observed the alteration of morphology in the lung of rats in the control group(20 rats) ,the DM group(30 rats)using spectroscopic analysis. The collagen accumulation of lung was observed by masson trihrome staining, and alteration of NF-κB P65, IκBα, and PKC in lung was observed by immunohistochemistry. Results The tissue structure of lung in the DM rats distributed deranged in the light microscope, alveolar wall were thicken, extracellular matrixes increased and pulmonary fibrosis appeared. With the development of pathogenic condition, the expression increased obviously. The staining optical density value of NF-κB P65 in tissue of lung in the 12 w and 24 w DM group were 0. 20 ± 0. 01 and 0. 35 ± 0. 06 respectively, which was significantly higher than those of the control group at the corresponding time point ( 0. 12 ± 0. 02 and 0. 17 ± 0. 03, respectively, Ps ＜ 0. 0l ). The staining optical density value of IκB in tissue of lung in the 12 w and 24 w DM group were 0. 29 ±0. 02 and 0. 36 ± 0. 03, respectively, which were significantly higher than those of the control at the corresponding time point (0. 08 ± 0. 02 and 0. 22 ± 0. 08, respectively, Ps ＜ 0. 01 ). Conclusion The signaling pathway of NF-κB/IκB participate in the occurrence and development in the pathogenesis of lung in DM, and may be one of the mechanisms of lung injury.

Pathological ultrastructure changes of lung tissue in diabetic rat and the preventive effect of rosiglitazone intervention / 中国综合临床

Objective To observe the pathological infrastructure changes of lung tissue in diabetic rat with pulmonary fibrosis and the preventive effect of rosiglitazone intervention. Methods The experimental type 2 diabetic rats were yielded by high-sugar, high fat diet plus intraperitoneal injecting streptozotocin (STZ). The pathological infrastructure changes of lung tissue were observed by transmission electron microscopy in the control, diabetes mellitus group and rosiglitazone treatment group respectively, and the hydroxyproline contentswere determined simultaneously. Results We observed accumulation of collagen fibers and extracellular matrix in the lung tissue of simple diabetic rat, which indicated pulmonary fibrosis. The hydroxyproline contents were significantly higher in diatetes mellitus group when compared to the control at 12 weeks[ 0. 77 ± 0. 03μg/(mg·prot) vs.0.63 ±0.03 μg/(mg·prot)] and 20 weeks [0.93 ±0. 10 μg/(mg·prot) vs.0.87 ±0.10μg/ (mg·prot) ]. (Ps < 0.05) , but the rosiglitazone intervention significantly reduced the hydroxyproline 3contents in diabetes mellitus rats [0.85 ±0.08 μg/(mg·prot) vs.0.87 ±0. 10 μg/(mg·prot) ,P<0.05].Conclusion Pulmonary fibrosis occurred in diabetic rats lung tissue,while rosiglitazone can alleviate it.