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Objective@#To investigate the effects of insulin-like growth factor 1 receptor (IGF-1R) inhibitor on tubulopathy in diabetic kidney disease (DKD) mice.@*Methods@#C57BL/6J male mice were randomly divided into normal control group (n=10) and DKD model group (n=30), by giving a single intraperitoneal injection of STZ 150 mg/kg to establish a DKD model. After established successfully, the mice in DKD model group were randomly divided into DKD group (n=10), benazepril group (n=10) and IGF-1R inhibitor group (n=10). IGF-1R inhibitor group was given intraperitoneal injection of IGF-1R inhibitor (30 mg·kg-1·d-1) and benazepril group was given intraperitoneal injection of benazepril (30 mg·kg-1·d-1). Normal control group and DKD group were given an equal amount of normal saline. After 8 weeks of feeding, mice were euthanatized. Body weight and kidney weight were recorded. Blood, urine and kidney samples were collected. Biochemical tests such as blood glucose and urine albumin were measured by automatic biochemical instruments and albumin excretion rate was calculated. Pathological changes of mice were observed by hematoxylin-eosin staining (HE) and periodic acid-schiff staining (PAS). Phosph (p) IGF-1R expression level was determined by immunohistochemistry and Western blotting.@*Results@#Compared with the normal control group, blood glucose, kidney weight/body weight and urinary albumin excretion rate were significantly higher in DKD group (all P<0.01). In DKD mice, glomerular expansion, tubular stenosis, tubular swelling and tubular atrophy were significantly detected. Meanwhile, the number of proximal tubular epithelial (PTE) cells was decreased, and the renal tubular injury scores, the average glomerular volume, and pIGF-1R protein expression were increased (all P<0.05). Compared with the DKD group, albumin excretion rate was significantly reduced (P<0.01), the above pathological changes were alleviated and the effect of IGF-1R inhibitor was more significant. Compared with the DKD group, the pIGF-1R protein expression was reduced in IGF-1R inhibitor group (P<0.05). Compared with the benazepril group, the pIGF-1R protein expression was reduced in IGF-1R inhibitor group (P<0.05).@*Conclusion@#IGF-1R inhibitor has better effect than benazepril on alleviating the tubulopathy of DKD mice.
ABSTRACT
Objective To investigate the effects of insulin-like growth factor 1 receptor (IGF-1R) inhibitor on tubulopathy in diabetic kidney disease (DKD) mice.Methods C57BL/6J male mice were randomly divided into normal control group (n=10) and DKD model group (n=30),by giving a single intraperitoneal injection of STZ 150 mg/kg to establish a DKD model.After established successfully,the mice in DKD model group were randomly divided into DKD group (n=10),benazepril group (n=10) and IGF-1R inhibitor group (n=10).IGF-1R inhibitor group was given intraperitoneal injection of IGF-1R inhibitor (30 mg· kg-1· d-1) and benazepril group was given intraperitoneal injection of benazepril (30 mg· kg-1· d-1).Normal control group and DKD group were given an equal amount of normal saline.After 8 weeks of feeding,mice were euthanatized.Body weight and kidney weight were recorded.Blood,urine and kidney samples were collected.Biochemical tests such as blood glucose and urine albumin were measured by automatic biochemical instruments and albumin excretion rate was calculated.Pathological changes of mice were observed by hematoxylin-eosin staining (HE) and periodic acid-schiff staining (PAS).Phosph (p) IGF-1R expression level was determined by immunohistochemistry and Western blotting.Results Compared with the normal control group,blood glucose,kidney weight/body weight and urinary albumin excretion rate were significantly higher in DKD group (all P ＜ 0.01).In DKD mice,glomerular expansion,tubular stenosis,tubular swelling and tubular atrophy were significantly detected.Meanwhile,the number of proximal tubular epithelial (PTE) cells was decreased,and the renal tubular injury scores,the average glomerular volume,and plGF-1R protein expression were increased (all P ＜ 0.05).Compared with the DKD group,albumin excretion rate was significantly reduced (P ＜ 0.01),the above pathological changes were alleviated and the effect of IGF-1R inhibitor was more significant.Compared with the DKD group,the pIGF-1R protein expression was reduced in IGF-1R inhibitor group (P ＜ 0.05).Compared with the benazepril group,the pIGF-1R protein expression was reduced in IGF-1R inhibitor group (P ＜ 0.05).Conclusion IGF-1R inhibitor has better effect than benazepril on alleviating the tubulopathy of DKD mice.
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Objective To explore the role and mechanism of thymosin β4 (Tβ4) in the treatment of non-alcoholic fatty liver disease (NAFLD).Methods Forty male C57BL/J6 mice were divided into normal group,NAFLD group,low dose Tβ4 group and high dose Tβ4 group with 10 mice in each group.NAFLD mice model was established by feeding with high fat and high sugar diet for 16 weeks.The mice in low-dose Tβ4 group and high dose Tβ4 group were intraperitonealy injected with Tβ4 at 0.05 mg · kg-1 · d-1 and 0.20 mg · kg-1 · d-1,respectively,for eight weeks.The liver function indexes and serum tumor necrosis factor-α (TNF-α) level were detected;the pathological changes of liver tissue were observed under optical microscope and non-alcoholic fatty liver disease activity score (NAS) was evaluated.The protein expression levels of nuclear factor-κB p65 (NF-κB p65) and nuclear factor κB inhibit protein a (IκBa) at the protein level in liver tissue were measured by Western blotting method.The expression of TNF-α in liver tissue was detected by immunohistochemistry.Mean integral absorbance (MIA) was calculated.T test was performed for groups comparison.Results The levels of alanine aminotransferase (ALT),γ-glutamine transferase (GGT) and serum TNF-α levels of high dose Tβ4 group were all lower than those of NAFLD group ((28±17) U/L vs.(76±29) U/L,(61±39) U/L vs.(102±56) U/L,(144.1± 48.2) ng/L vs.(187.3±58.8) ng/L,respectively),and the differences were statistically significant (t=4.52,2.78 and 2.30,all P＜0.05).The NAS of low dose Tβ4 group and high dose Tβ4 group were both lower than that of NAFLD group (3.7±40.4,2.3±0.3 vs.4.6±0.3),and the differences were statistically significant (t=5.69 and 17.14,both P＜0.01).The relative expression level of Tβ4 protein of NAFLD group was lower than that of normal group (0.2±0.1 vs.1.4±0.6),and the difference was statistically significant (t=6.24,P＜0.01).The relative expression levels of Tβ4 and IκBa of high dose Tβ4 group were higher than those of NAFLD group (1.0±0.3,0.5±0.3 vs.0.2±0.1),and the differences were statistically significant (t=8.00 and 3.00,both P＜0.01).The relative expression level of NF-κB p65 in liver tissue of high dose Tβ4 group was lower than that of NAFLD group (0.6±0.3 vs.1.5±0.7),and the difference was statistically significant (t=3.74,P＜0.01).The MIA of high dose Tβ4 group was lower than that of NAFLD group (0.4±0.2 vs.0.7±0.3),and the difference was statistically significant (t=2.63,P＜ 0.01).Conclusion Tβ4 can effectively treat NAFLD probably through inhibiting the NF-κB pathway.
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Objective To investigate the allergens and study the clinical significance of detecting serum levels of TNF-α,IL-4, IL-6 and IL-8 in patients with bronchial asthma.Methods 62 cases of patients with bronchial asthma were selected from August 2011 to August 2013 in Baoji Central Hospital,enzyme-linked immunosorbent assay were carried out in patients u-sing standardized allergens.62 cases of healthy people were selected as control group,and detected serum levels of TNF-α, IL-4,IL-6 and IL-8 of the two groups.Results Dust mites were the most important and the strongest allergens.The levels of TNF-α,IL-4,IL-6 and IL-8 in observation group was significantly higher than those in control group (230.87±27.82 ng/ml vs 152.14± 23.27 ng/ml;25.32 ± 12.04 ng/L vs 8.57 ± 3.64 ng/L;152.45 ± 24.56 μg/L vs 98.56 ± 18.63 μg/L;218.79±32.91μg/L vs 142.68±23.76μg/L,P<0.05).Conclusion TNF-α,IL-4,IL-6 and IL-8 levels in patients with bronchial asthma j udgment can be used as an important predictor,and it is worthy of clinical application.
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The clinical data of 186 patients with acute gout attack during upper gastrointestinal bleeding were analyzed retrospectively.The ratio of male to female was 1.7∶1, smokers and alcohol drinkers accounted for 66.1% ( 123/186 ) and 62.4% ( 116/186 ) of patients were had underlying diseases.All patients had different degree of joint painful and fever , the blood uric acid levels were higher.Gastroscopic examinations were performed in 166 patients , of whom 88 cases received endoscopic intervention.The symptoms of gout were improved after treatment with dexamethasone and celecoxib ; and the medication did not induce or increase gastrointestinal bleeding.
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This report presented a case of 62-year-old woman who was admitted to our hospital for cirrosis, but she had a variety of clinical manifestations,such as abdominal distension,diarrhea,ascites, hepatosplenomegaly,anemia, palpitation, flushing, low blood pressure, arrhythmia and so on. Upper gastrointestinal endoscopy showed thicken mucosa at gastric fundus. Colonoscopy revealed nodular, pseudopolypoid. Ascitic fluid test suggested a transudate. Endoscopic abnormal mucosa biopsy showed chronic inflammation. Many mast cells were seen in bone marrow and liver biopsies,and liver tissue immunophenotype was CD117, and CD68. Thus the patient's diagnosis was systemic mastocytosis. It is rare that a patient only has the gastrointestinal tract symptoms complicated with ascites without skin lesion. The goal for treatment was to reduce hypersecretion of mast cells.