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ObjectiveTo investigate the intervention effect of Jiedu Tongluo Tiaogan prescription （JTTP） in protecting pancreatic β cells by targeting the bile acid Takeda G protein-coupled receptor 5 （TGR5）/cyclic adenosine monophosphate （cAMP） signaling pathway against NOD-like receptor protein 3 （NLRP3） inflammasome. MethodThirty-two male SPF-grade db/db mice were randomly divided into the model group， low-dose JTTP group （3.6 g·kg-1）， high-dose JTTP group （7.2 g·kg-1）， and metformin group （0.2 g·kg-1）. Eight db/m mice were assigned to the blank control group. The mice were treated with drugs for 8 weeks， and fasting blood glucose （FBG） was measured every 2 weeks. Oral glucose tolerance tests （OGTT） were conducted after the last administration. Enzyme-linked immunosorbent assay （ELISA） was performed to detect fasting insulin （FINS）， and the homeostasis model assessment of β-cell function （HOMA-β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and IL-1β levels were calculated. Hematoxylin-eosin （HE） staining was used to observe pathological changes in mouse pancreatic tissue. Immunofluorescence was performed to detect insulin expression in mouse pancreatic tissue. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of proteins and mRNAs of key targets in the TGR5/cAMP signaling pathway and NLRP3 inflammasome. ResultCompared with blank group， FBG， OGTT， FINS， IL-6， TNF-α and IL-1β in model group were significantly increased （P<0.01）. Compared with model group， after 6 weeks of drug treatment， FBG level in JTTP group and metformin group decreased significantly （P<0.01）. The results of OGTT experiment showed that compared with model group， the blood glucose levels of mice in each administration group were decreased at all time points （P<0.05， P<0.01）， and the levels of FINS， TNF-α and IL-6 in JTTP dose groups and metformin group were significantly decreased. The level of IL-1β in JTTP high-dose group and metformin group was significantly decreased （P<0.01）. Pancreatic pathology showed that the islets in the model group were irregular in shape， uneven in distribution， and showed signs of atrophy. The prognosis of JTTP was that the cell count increased and the boundary was clearer. Immunofluorescence results showed that the islet cells in the blank group were arranged in an orderly and full shape with appropriate insulin secretion， while the islet cells in model group were distorted in shape， atrophy in structure and less insulin secretion. The insulin content of mice in JTTP and metformin group was significantly increased. Compared with blank group， mRNA expressions of NLRP3， apoptosis-related spot-like protein （ASC） and Caspase-1 in pancreatic tissues of model group were significantly increased （P<0.01）. Compared with model group， JTTP high-dose group and metformin group promoted the up-regulation of TGR5 and cAMP mRNA， and down-regulated the mRNA expressions of NLRP3， ASC and Caspase-1 （P<0.05， P<0.01）. Compared with blank group， the expression of TGR5 protein in model group was significantly decreased （P<0.01）. Compared with model group， TGR5 protein in JTTP high-dose group and metformin group was significantly increased （P<0.01）.
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Objective To study the incidence and risk factors of new foot ulcer among diabetic patients on peritoneal dialysis.Methods This is a single-center prospective cohort study.Clinically-stable diabetic patients on peritoneal dialysis in our renal division were recruited from January 2014 to June 2014.Baseline data including general information,biochemistry data,dialysis adequacy,the dorsalis pedis artery pulse,clinical symptoms of diabetic foot and ankle brachial index were recorded.All patients were followed till to Dec 31,2015.The outcomes consisted of new foot ulcer,amputation due to foot ulcer or gangrene,and lower limb vascular blood supply revascularization.Results Totally 108 patients were recruited and followed up the average time (17.7±5.6) months.Among 108 patients,16 cases had a history of diabetic foot ulcer,and 1 case had amputation.During the follow-up,11 cases (10.2％) had new foot ulcer,3 cases (2.8％) had amputation due to foot ulcers or gangrene,and 8 cases (7.4％) had lower limb vascular blood supply revascularization.A total of 13 cases (12％) had composite end points with 81.3 times/1000 patients of incidence.Univariate and multivariate Cox regression models showed that the history of foot ulcer was the only independent risk factors for new foot ulcers-related composite end points.Conclusion The incidence of new foot ulcer-related composite end points was 12％,which could be independently predicted by the history of diabetic foot ulcer.
ABSTRACT
Objective To study the incidence and risk factors of new foot ulcer among diabetic patients on peritoneal dialysis.Methods This is a single-center prospective cohort study.Clinically-stable diabetic patients on peritoneal dialysis in our renal division were recruited from January 2014 to June 2014.Baseline data including general information,biochemistry data,dialysis adequacy,the dorsalis pedis artery pulse,clinical symptoms of diabetic foot and ankle brachial index were recorded.All patients were followed till to Dec 31,2015.The outcomes consisted of new foot ulcer,amputation due to foot ulcer or gangrene,and lower limb vascular blood supply revascularization.Results Totally 108 patients were recruited and followed up the average time (17.7±5.6) months.Among 108 patients,16 cases had a history of diabetic foot ulcer,and 1 case had amputation.During the follow-up,11 cases (10.2％) had new foot ulcer,3 cases (2.8％) had amputation due to foot ulcers or gangrene,and 8 cases (7.4％) had lower limb vascular blood supply revascularization.A total of 13 cases (12％) had composite end points with 81.3 times/1000 patients of incidence.Univariate and multivariate Cox regression models showed that the history of foot ulcer was the only independent risk factors for new foot ulcers-related composite end points.Conclusion The incidence of new foot ulcer-related composite end points was 12％,which could be independently predicted by the history of diabetic foot ulcer.
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Objective: Elsibucol is a metabolically stable derivative of probucol with the properties of anti-oxidation, anti-inflammation and anti-proliferation. We want to explore the effect of elsibucol on abdominal aorta injury in hypercholesterolemia rabbits. Methods: A total of 45 male New Zealand rabbits were divided into 3 groups: Control group, the rabbits were fed by high cholesterol diet, Elsibucol group, the rabbits received high cholesterol diet with 1% elsibucol and Probucol group, the rabbits received high cholesterol diet with 1% probucol.n=15 in each group. All animals were treated for 2 weeks followed by the procedure of abdominal aortic balloon injury and then, drug therapy was continued for 10 weeks. The area and load of atherosclerosis in abdominal aorta were evaluated by IVUS, the amount of macrophages in plaque were observed by immunohistochemistry, mRNA and protein expressions of MCP-1, MMP-9 were examined by RT-PCR and immunohistochemistry. Results: Compared with Control group, Elsibucol group showed decreased blood LDL-C and oxidative stress, decreased amount of macrophages and lower expression of inlfammatory factors in atherosclerosis plaque, reduced plaque area and load, allP<0.01. Compared with Probucol group, Elsibucol group presented even lower plaque area and load, allP<0.01. Conclusion: Elsibucol inhibits the progress of atherosclerosis in experimental rabbits via regulating blood lipids, anti-inlfammation and anti-oxidation.
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Objective To investigate the anti-inflammatory effect of C1q/ tumor necrosis factor (TNF)-related protein 9 (CTRP9) in RAW264.7 mouse macrophage cells treated with oxidized low density lipoprotein (oxLDL),and to explore its mechanism.Methods RAW264.7 mouse macrophage cells were divided into three groups:the control group,the oxLDL group (treated with oxLDl) and the gCTRP9-oxLDL group (pretreated with recombinant globular domain of CTRP9 and stimulated by oxLDL).Foam cells were detected by oil red O staining.Western blot was used to detect the expressions of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein 1 (MCP-1).In addition,the expression levels of NF-κB p65 in cytoplasm and nucleus proteins extraction were both determined.Results The relative levels of MCP-1 and NF-κB were increased in the oxLDL group as compared with the control group (1.66±0.09 vs.1.03±0.10,0.52±0.11 vs.1.03±0.06,both P＜0.05).The expression levels of TNF-α and MCP-1 were decreased in gCTRP9+oxLDL group as compared with the oxLDL group (both P＜0.05).The expression level of NF κB p65 in nucleus 2 and 8 h after treatment was lower in the gCTRP9+oxLDL group than in the oxLDL group (1.03±0.06 vs.0.17±0.10,0.31±0.03,both P＜0.05).Conclusions oxLDL may induce the expressions of inflammatory cytokines of TNF α and MCP-1 in macrophage ceils.gCTRP9 pretreatment could reduce the oxLDL-induced pro inflammatory effect and nuclear factor κB translocation may be involved in this process,which suggests that gCTRP9 may play a protective role in anti inflammatory and anti-atherosclerosis.