1.Pathogenesis of diseases with antineutrophil cytoplasmic antibody and its clinical significance
Chinese Journal of Primary Medicine and Pharmacy 2017;24(2):279-282
Objective To investigate the pathogenesis of diseases with antineutrophil cytoplasmic antibody (ANCA)and its diagnostic value in primary small vessel vasculitis.Methods 57 patients with serum ANCA positive were involved in this study,and ELISA was employed to assay anti-MPO.Patients with ANCA positive,anti-MPO positive and/or anti-PR3 positive were involved in group A.Patients with ANCA positive,anti-MPO negative and anti-PR3 negative were involved in group B.X2 was used to analyze the differences between the two groups.Results The etiology of 57 ANCA positive patients included primary small vessel vasculitis (20 cases,35.1%),non inflam-matory connective tissue disease(19 cases,33.3%),non connective tissue disease(18 cases,31.6%).A group of primary small vessel vasculitis accounted for 58.6%,which was significantly higher than 10.7% of the B group (χ2 =14.354,P<0.01);while the B group of non inflammatory connective tissue disease accounted for 50%,which was significantly higher than 17.2%of the A group (χ2 =6.879,P<0.01).Conclusion ANCA should be found in many kinds of diseases,so combined detection of anti-MPO and anti-PR3 should be employed to improve the diag-nosis specificity in primary small vessel vasculitis.Furthermore,non vessel vasculitis connective tissue disease should be excluded in patients with ANCA positive,anti-MPO and anti-PR3 negative.
2.Effect of angiotensin Ⅱ type 1 receptor blocker on the 12-lipoxygenase activity and P-cadherin expression in type 2 diabetic rat glomeruli
Wanning WANG ; Jia LI ; Fuzhe MA ; Tao SUN ; Mindan SUN ; Zhonggao XU
Chinese Journal of Nephrology 2013;(3):210-215
Objective To investigate the effect of angiotensin Ⅱ (Ang Ⅱ) type 1 receptor blocker (ARB) on 12-lipoxygenase (12-LO) activity and P-cadherin expression in type 2 diabetic rat glomeruli.Methods Podocytes were stimulated by 107 mol/L Ang Ⅱ for 24 hours.12(S)-HETE (1mg· kg 1 · d-1) and Ang Ⅱ (400 ng· kg-1· min-1) were infused to rats by osmotic mini-pump for 1 week and 2 weeks respectively.Rats fed with high fat diet received low dose streptozotocin (STZ) to make type 2 diabetes and divided into 2 groups:low dose STZ (DN group),low dose STZ + ARB treatment (Losartan group).Rats fed with regular chow were used as control group.All the rats were sacrificed after 6 weeks.Urine,blood,kidney cortical tissue and isolated glomeruli by sieving method were collected at the end of study respectively.ELISA,RT-PCR and Western blotting for related target were performed respectively.Results Ang Ⅱ increased 12(S)-HETE levels in podocytes and glomeruli (all P < 0.01).Ang Ⅱ levels in the glomeruli were significantly increased by 12(S)-HETE stimulation (P <0.01).Blood glucose,kidney/body weight and 24 hour urinary protein were increased in DN group compared with that in control group (all P < 0.01).However,urine protein,Kidney/body weight were decreased in Losartan group compared with DN group (all P < 0.05).Increment of 12(S)-HETE content and decrement of P-cadherin expression were observed in DN glomeruli compared with that in control group(all P < 0.01).These abnormalities were prevented by administration of the losartan (all P < 0.05).Conclusions Ang Ⅱ can down-regulate glomerular P-cadherin expression via activation of 12-LO.ARB can ameliorate the progression of DN via up-regulation of glomerular P-cadherin through inhibition of 12-LO activation in type 2 DN rats.
3.Pathogen profile and risk factors of infected diabetic foot ulcers
Hong LIN ; Xiaoqing WANG ; Lihui HUANG ; Mindan XU ; Lin MA ; Renxu LAI
Chinese Journal of Infection and Chemotherapy 2017;17(1):14-18
Objective To explore and analyze the pathogen proifle and risk factors of infected diabetic foot ulcers, and propose appropriate prevention and intervention measures for early recovery of patients.Methods The data of 120 patients with diabetic foot ulcers treated in our hospital from February 2012 to May 2014 were retrospectively analyzed. These patients were classified into infection group (38 patients) and non-infection group (82 patients) based on whether their ulcer was infected or not. The pathogens and risk factors of infection in diabetic foot ulcer were analyzed.Results In this study, 43 strains of pathogenic bacteria were isolated from 38 cases of infection, of which gram positive bacteria accounted for 51.2 %, gram negative bacteria 41.9 %, and fungi 7.0 %.Staphylococcus aureus,Pseudomonas aeruginosa and Enterobacter cloacae were the top three pathogens, accounting for 16.3 % each. Univariate analysis showed that diabetic vascular complication, retinopathy, more than 2 foci of ulcer, osteomyelitis, and diabetic nephropathy were closely associated with infection (P<0.05). Multivariate logistic regression analysis showed that HDL-C, albumin, diabetic vascular complication, number of ulcers, osteomyelitis were independent risk factors for infection in patients with diabetic foot ulcer. Conclusions HDL-C, red blood cell, hemoglobin, diabetic complications, white blood cell, triglyceride, albumin, diabetic vascular complication and smoking are the risk factors for infection in patients with diabetic foot ulcer. These factors should be prevented and controlled to reduce the incidence of infection in diabetic foot ulcer.
4.Effects of 12-lipoxygenase and angiotensin Ⅱ on p21, p27 and p57 in rat diabetic glomeruli
Chongsen ZANG ; Wanning WANG ; Ye JIA ; Fuzhe MA ; Tao SUN ; Mindan SUN ; Weixia SUN ; Hang YUAN ; Zhonggao XU
Chinese Journal of Nephrology 2017;33(2):132-139
Objective To investigate the effects of 12-lipoxygenase (12-LO) and angiotensin Ⅱ (Ang Ⅱ) on the CIP/KIP family of cyclin-dependent kinase inhibitors (CKIs) p21,p27 and p57 related to cell hypertrophy.Methods Mesangial cells were treated with high glucose for 24 hours and 48 hours respectively.12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] and Ang Ⅱ were infused to rats by osmotic mini-pump for 1 week and 2 weeks respectively.Rats fed high fat diet were received low dose streptozotocin (STZ) to make type 2 diabetes (DN).The rats were divided into normal control group,DN group,DN+Ang Ⅱ type 1 receptor blocker (ARB) group or 12-LO inhibitor (CDC) group.DN+ARB rats were treated by losartan for 6 weeks,and DN+CDC rats were treated for 8 weeks.Urine albumin and protein expressions of p21,p27 and p57 were detected by ELISA and Western blotting respectively.Glomeruli injury and expressions of p21 and p27 were detected by PAS staining and immunohistochemistry respectively.Results High glucose increased p21 and p27 protein expression in mesangial cells significantly compared with the relative control (all P < 0.05),but had no effect on p57.Ang Ⅱ increased p27 protein expression in gloneruli significantly (P < 0.05),but had no effect on p21 and p57 protein expression.12(S)-HETE increased both p21 and p27 protein expression in glomeruli significantly (all P < 0.05),but had no effect on p57 protein expression.Blood glucose,kidney/body weight,urinary protein,and glomerular p21 and p27 protein expressions were increased in DN group (all P < 0.05) compared with those in control group,with little change of p57 protein expression (P < 0.05).Moreover,glomerular hypertrophy and extra cellular matrix accumulation were observed in DN group.However,urine protein,kidney/body weight,renal injury,but not blood glucose,were decreased in DN+ARB group and DN+CDC group compared with DN group respectively (P< 0.05).Further DN+CDC rats had decreased both p21 and p27 protein expressions in glomeruli,but DN+ ARB rats only had decreased p27 protein expression (all P < 0.05).Conclusions 12-LO may induce both p21 and p27 protein expression in DN glomeruli,but Ang Ⅱ may induce only p27 expression.
5.The role of PCSK9 on lipid accumulation and injury in the kidney of C57BL/6 mice
Meiyan WU ; Chongsen ZANG ; Fuzhe MA ; Bin CHEN ; Weixia SUN ; Mindan SUN ; Hang YUAN ; Zhonggao XU ; Ye JIA
Chinese Journal of Nephrology 2018;34(11):845-850
Objectives To evaluate the role of PCSK9 (proprotein convertase subtilisin kexin type 9) on the lipid accumulation and kidney injury of C57BL/6 mice. Methods The 24 h urine of 12 weeks old wide type C57BL/6 mice and PCSK9 knockout (KO) mice were collected through a metabolic cage, followed by perfusion and sacrifice. Urinary microalbumin?to?creatinine ratio (UACr), total cholesterol and triglyceride in kidney tissues were measured by ELISA. BODIPY 493/503 staining and standard transmission electron microscopy (TEM) of kidney tissues was performed for evaluating lipid accumulation and podocyte foot effacement in the kidney. Kidney tissues were also evaluated by PAS stain and TUNNEL stain. PCSK9, podocin and nephrin were quantified through real?time PCR, and the Bcl?2, Bax and cleaved caspase 3 were evaluated by Western blotting. Results Total cholesterol and triglyceride contents were higher in the kidneys of PCSK9 KO mice than controls (P<0.05). The level of lipid accumulation in glomeruli and tubules through BODIPY 493/503 stain, and the amount of lipid drop in TEM were more serious in PCSK9 KO mice. UACr and podocyte foot process effacement were increased, and the transcription of podocin and nephrin were decreased in the kidneys of PCSK9 KO mice (all P<0.05). The expression of Bcl?2 was decreased, and Bax and cleavedcaspase 3 were increased in the kidney samples of PCSK9 KO mice. Conclusion PCSK9 might be reversely involved in lipid homeostasis and accumulation, resulting in injury and apoptosis in the kidneys of C57BL/6 mice.