Effect of naringin on oxidative stress and endoplasmic reticulum stress in diabetic cardiomyopathy / 中国中药杂志

To explore the protective effect of naringin(Nar) on the injury of myocardium tissues induced by streptozotocin(STZ) in diabetic rats and the relationship with oxidative stress and endoplasmic reticulum stress(ERS)， the male SD rats were intraperitoneally injected with streptozotocin(STZ， 60 mg·kg⁻¹) to establish the diabetic rat model and then randomly divided into the type 1 diabetic rat group(T1DR)， the low-dose Nar group(Nar25)， the middle-dose Nar group(Nar50) and the high-dose Nar group(Nar100). The normal rats were designed as control group(Con). Nar25， Nar50， Nar100 groups were orally administered with Nar at the doses of 25.0， 50.0， 100.0 mg·kg⁻¹ per day， respectively， while the normal group and the T1DR group were orally administered with saline. At the 8th week after treatment， fasting plasma glucose and heart mass index were measured. The pathological changes in myocardial tissues were observed by microscope. The cardiac malondialdehyde(MDA) level and superoxide dismutase(SOD) activities were measured. The gene and protein expressions of glucose-regulated protein 78(GRP78)， C/EBP homologous protein(CHOP)， cysteinyl aspartate-specific proteinase 12(caspase 12) were detected by qRT-PCR and Western blot. According to the results， compared with control group， the myocardial structure was damaged， the content of MDA was increased， while the activities of SOD were decreased(<0.05) in T1DR group. GRP78， CHOP and caspase 12 mRNA and protein expressions were increased significantly in T1DR group(<0.05， <0.01). Compared with T1DR group， myocardial structure damage was alleviated in Nar treatment group. The content of MDA was decreased， while the activities of SOD were increased significantly. The mRNA and protein expressions of GRP78， CHOP and caspase 12 were increased， especially in middle and high-dose groups(<0.05， <0.01). After treatment with Nar for 8 weeks， myocardial structure damage was obviously alleviated in Nar treatment groups. The content of MDA was decreased， while the activities of SOD were increased significantly in myocardial tissues. The mRNA and protein expressions of GRP78， CHOP and caspase 12 were increased， especially in middle and high-dose groups(<0.05， <0.01). The findings suggest that Nar may protect myocardium in diabetic rats by reducing mitochondrial oxidative stress injuries and inhibiting the ERS-mediated cell apoptosis pathway.

Effects of Fritillariae Cirrhosae Bulbus on MMP-2,MMP-9 and TIMP-1 in murine asthma model / 中国中药杂志

To investigate the effects of Fritillariae Cirrhosae Bulbus on airway remodeling and matrix metalloproteinase-2(MMP-2), matrix metalloproteinase-9(MMP-9), tissue inhibitor-1 of metalloproteinase(TIMP-1) of a murine asthma model, and explore its mechanism in treatment of asthma. BALB/C murines were randomly divided into the normal group, model group, high dose group, low dose group, and positive control group. Except for the normal group, all the other groups received ovalbumin(OVA) to establish murine asthma model. After successful modeling, the murines in high dose group and low dose group were orally administered with Fritillariae Cirrhosae Bulbus powder at the dose of 18.0 mg•kg⁻¹ and 9.0 mg•kg⁻¹, respectively; the murines in positive control group were injected intraperitoneally with dexamethasone at the dose of 0.5 mg•kg⁻¹; while the murines in normal group and the model group were orally administered with the same volume of normal saline. All the drugs were given to murines per day for 28 d. The variations of airway responsiveness, variations of the total cell count and leukocyte differential count in bronchoalveolar lavage fluid(BALF), and the variations of thicknesses of bronchial wall and airway smooth muscle of each group were observed. The levels of MMP-2, MMP-9 and TIMP-1 were measured by ELISA; and the expression levels of MMP-2, MMP-9 and TIMP-1 mRNA were detected by RT-PCR. The results showed that as compared with the normal group, the airway responsiveness, the count of total cells, neutrophils, macrophage, lymphocytes, eosinophils in BALF, and the thicknesses of bronchial wall and airway smooth muscle were increased significantly in the model group(P<0.01); as compared with the model group, the above indicators were decreased significantly in the high dose group, low dose group and positive control group (P<0.05 or P<0.01). As compared with the normal group, the levels and expressions of MMP-2, MMP-9 and TIMP-1 mRNA were increased significantly in the model group(P<0.01); while as compared with the model group, these levels were decreased significantly in the high dose group, low dose group and positive control group(P<0.01). In conclusion, Fritillariae Cirrhosae Bulbus can improve airway remodeling in a murine asthma model, and its mechanisms may be related to down-regulating MMP-2, MMP-9 and TIMP-1 levels.

Morphology of Hypertrophic Scar Tissues and Expressions of Vascular Endothelial Growth Factor and Transforming Growth Factor Beta Activated Kinase 1 in These Tissues / 中国医学科学院学报

<p><b>OBJECTIVE</b>To observe the morphology of hypertrophic scar tissue and explore the expressions and distribution of vascular endothelial growth factor (VEGF) and transforming growth factor beta activated kinase 1(TAK1 )in these tissues.</p><p><b>METHOD</b>Hematoxylin-eosin staining, Masson staining,immunofluorescence,and real-time polymerase chain reaction were used to detect the localization and expression of VEGF and TAK1 in 15 hypertrophic scar tissues and 10 normal skin tissues.</p><p><b>RESULTS</b>Morphological observation showed that the dermal fibroblasts in hypertrophic scar were disorderly and densely arranged (compared to the normal skin). Immunofluorescence displayed that the expressions of VEGF and TAK1 in hypertrophic scar tissue were higher than in normal skin tissues. Real-time polymerase chain reaction showed the mRNA expressions of both VEGF and TAK1 were significantly higher in hypertrophic scar tissue than in normal tissue (P<0.01, P<0.05,respectively).</p><p><b>CONCLUSIONS</b>Hypertrophic scar tissue has higher collagen fibrosis degree and higher TAK1 and VEGF expressions than the normal skin. VEGF and TAK1 can be used as the reference indicators for the diagnosis and differential diagnosis of hypertrophic scar and serve as new therapeutic targets.</p>