Background Insulin resistance (IR) is present at all stages of chronic kidney disease (CKD) and is associated with CKD progression. Probueol can improve the prognosis of IR in diabetes mellitus (DM) patients. Th...Background Insulin resistance (IR) is present at all stages of chronic kidney disease (CKD) and is associated with CKD progression. Probueol can improve the prognosis of IR in diabetes mellitus (DM) patients. This study aimed to observe the effect of probucol on IR and kidney protection in non-diabetic CKD patients. Methods This was an open-label, non-placebo-controlled, randomized study. A total of 59 patients were randomized to the probucol group (0.5 g, twice daily) or the control group using a 1: 1 treatment ratio. IR was determined using a homeostatic model assessment-IR (HOMA-IR) index. An Excel database was established to analyze foUow-up data at weeks 0, 12, and 24. The primary outcome of interest was changes in the HOMA-IR, and the secondary outcomes of interest were changes in the estimated glomerular filtration rate (eGFR), body mass index (BMI), cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and 24-h urinary protein. Results The HOMA-IR index of the probucol group after 24 weeks was significantly decreased (P 〈 0.001) compared to the value before treatment (average decrease: 1.45; range: -2.90 to -0.43). The HOMA-IR index in the control group increased (average increase: 0.54; range: -0.38 to 1.87). For the secondary outcomes of interest, the changes between these two groups also exhibited significant differences in eGFR (P = 0.041), cholesterol (P = 0.001), fasting insulin (P 〈 0.001), and fasting C-peptide (P = 0.001). Conclusions Compared to angiotensin receptor blockers alone, the combination with probucol ameliorates IR in non-diabetic CKD patients and delays disease progression.展开更多
Type 2 diabetes (T2D) is common in the elderly and more than half of the people with diabetes are over 65 years old. Elderly diabetic patients have a higher frequency of hypertension, coronary artery disease and chr...Type 2 diabetes (T2D) is common in the elderly and more than half of the people with diabetes are over 65 years old. Elderly diabetic patients have a higher frequency of hypertension, coronary artery disease and chronic kidney disease than non-diabetic elderly patients and the risk of these complications increases with patient age, duration of the dia- betes and glycated hemoglobin values. Besides the known classical factors of renal disease progression,展开更多
Objective Our objective was to analyze the traditional Chinese medicine(TCM)syndrome and treatment laws of diabetic kidney disease(DKD)and the action mechanism of high-frequency Chinese herbs in the treatment of DKD b...Objective Our objective was to analyze the traditional Chinese medicine(TCM)syndrome and treatment laws of diabetic kidney disease(DKD)and the action mechanism of high-frequency Chinese herbs in the treatment of DKD based on realworldstudy.MethodsThe data of patients with DKD who had been treated in the First Hospital Affiliated to Henan Universityof ChineseMedicine from January1,2014to December 31,2021 were retrospectively analyzed through the hospital information management system.The contents of the cases were statistically analyzed using IBM SPsS Statistics 25 software,and the laws of DKDtreatment were summarized.Network pharmacology and molecular docking were used to analyze the action mechanism of high-frequency Chinese herbs in the treatment of DKD.ResultsThe data of a total of 1,201 patients with DKD were included,involving 72 kinds of TCM syndromes.Nine disease nature elements and six disease location elements were extracted,involving 405 Chinese herbs.The top five high-frequency Chinese herbs were Baizhu(Atractylodis Macrocephalae Rhizoma),Fuling(Poria),Huangqi(Astragali Radix),Chuanxiong(Chuanxiong Rhizoma),and Danshen(Salviae Miltiorrhizae Radix et Rhizoma).Thirty kinds of Chinese herbs with the frequency of≥100 were mainly deficiency-tonifying herbs and blood-activating and stasis-eliminating herbs.The medicinal properties were mainly warm and mild,and the medicinal flavors were sweet and bitter mostly.For the meridian tropism,the main meridian tropism of these herbs is spleen meridian and lung meridian.The clustering method.展开更多
Objective To investigate the renoprotection effect of low molecular weight heparin(LMWH)in diabetic rats.Methods Diabetic rats were induced by injection of steptozotocin(STZ).Rats were randomly divided into three grou...Objective To investigate the renoprotection effect of low molecular weight heparin(LMWH)in diabetic rats.Methods Diabetic rats were induced by injection of steptozotocin(STZ).Rats were randomly divided into three groups:control group,diabetic model group,and LMWH treatment group.The levels of total cholesterol(TC),triglyceride(TG),prothrombin time(PT),kaolin partial thromboplastin time(KPTT),24-hour urinary albumin excretion rate(UAER),and serum soluble P-selectin were determined after 8 weeks.Glomerular morphology was observed by light microscopy.Results The levels of TG,UAER,and P-selectin in LWMH treatment group were lower than those in model group(all P<0.01).The levels of PT and KPTT in LWMH treatment group were shorter than those in model group.And LWMH improved the histological changes of diabetic rats.Conclusion LMWH has some renal protective effects in diabetic rats,partly through down-regulating the expression of P-selectin.展开更多
OBJECTIVE: To investigate the effects of the mixed endothelin receptor antagonist, bosentan, combined with the long-acting calcium channel blocker, amlodipine, compared to the angiotensin-converting enzyme inhibitor, ...OBJECTIVE: To investigate the effects of the mixed endothelin receptor antagonist, bosentan, combined with the long-acting calcium channel blocker, amlodipine, compared to the angiotensin-converting enzyme inhibitor, cilazapril, on the progressive renal injury in spontaneous hypertensive rats (SHR) with diabetes. METHODS: Diabetic hypertensive rats (SHR-DM) were induced by streptozotozin injected in male SHR (7-week-old),and divided into an untreated and three treated groups: 1) cilazapril treated group; 2) bosentan+amlodipine treated group; and 3) amlodipine treated group. Wistar Kyoto rats (WKY) and SHR rats served as normotensive and hypertensive control, respectively. The mean arterial blood pressure, renal function, endothelin and angiotensin II levels as well as the protein expression of renal extracellular matrix components and transforming growth factor (TGF)-beta1 were determined at the end of the 4th week. RESULTS: Mean arterial blood pressure significantly increased in SHR and SHR-DM rats compared to WKY rats. All the therapies reduced the blood pressure to normal levels. However, the enhanced urinary protein excretion, the decreased creatinine clearance as well as the increased plasma and intrarenal endothelin and angiotens in II levels were found in the untreated SHR-DM and prevented by treatment with bosentan+amlodipine and cilazapril. Similarly, these two kinds of therapies in SHR-DM abolished the overexpression of renal TGF-beta1 by Western blot analysis and reduced the accumulation of collagen type IV, laminin and fibronectin proteins by an immunochemical approach. Amlodipine monotherapy had no detectable effects on the above parameters. CONCLUSION: Bosentan combined with amlodipine can offer similar renoprotective effects on that of cilazapril and may be a potent therapy to attenuate renal injury by reducing renal protein levels of TGF-beta1 in diabetes with a hypertensive state.展开更多
Nephrin is a key molecule in podocytes to maintain normal slit diaphragm structure. Nephin interacts with many other podo- cyte and slit diaphragm protein and also mediates important cell signaling pathways in podocyt...Nephrin is a key molecule in podocytes to maintain normal slit diaphragm structure. Nephin interacts with many other podo- cyte and slit diaphragm protein and also mediates important cell signaling pathways in podocytes. Loss of nephrin during the development leads to the congenital nephrotic syndrome in children. Reduction of nephrin expression is often observed in adult kidney diseases including diabetic nephropathy and HIV-associated nephropathy. The critical role of nephrin has been confirmed by different animal models with nepbrin knockout and knockdown. Recent studies demonstrate that knockdown of nephrin expression in adult mice aggravates the progression of' unilateral nephrectomy and Adriamycin-induced kidney disease In addition to its critical role in maintaining normal glomerular filtration unit in the kidney, nephrin is also expressed in other organs. However, the exact role of nephrin in kidney and extra-renal organs has not been well characterized. Future studies are required to determine whether nephrin could be developed as a drug target to treat patients with kidney disease.展开更多
文摘Background Insulin resistance (IR) is present at all stages of chronic kidney disease (CKD) and is associated with CKD progression. Probueol can improve the prognosis of IR in diabetes mellitus (DM) patients. This study aimed to observe the effect of probucol on IR and kidney protection in non-diabetic CKD patients. Methods This was an open-label, non-placebo-controlled, randomized study. A total of 59 patients were randomized to the probucol group (0.5 g, twice daily) or the control group using a 1: 1 treatment ratio. IR was determined using a homeostatic model assessment-IR (HOMA-IR) index. An Excel database was established to analyze foUow-up data at weeks 0, 12, and 24. The primary outcome of interest was changes in the HOMA-IR, and the secondary outcomes of interest were changes in the estimated glomerular filtration rate (eGFR), body mass index (BMI), cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and 24-h urinary protein. Results The HOMA-IR index of the probucol group after 24 weeks was significantly decreased (P 〈 0.001) compared to the value before treatment (average decrease: 1.45; range: -2.90 to -0.43). The HOMA-IR index in the control group increased (average increase: 0.54; range: -0.38 to 1.87). For the secondary outcomes of interest, the changes between these two groups also exhibited significant differences in eGFR (P = 0.041), cholesterol (P = 0.001), fasting insulin (P 〈 0.001), and fasting C-peptide (P = 0.001). Conclusions Compared to angiotensin receptor blockers alone, the combination with probucol ameliorates IR in non-diabetic CKD patients and delays disease progression.
文摘Type 2 diabetes (T2D) is common in the elderly and more than half of the people with diabetes are over 65 years old. Elderly diabetic patients have a higher frequency of hypertension, coronary artery disease and chronic kidney disease than non-diabetic elderly patients and the risk of these complications increases with patient age, duration of the dia- betes and glycated hemoglobin values. Besides the known classical factors of renal disease progression,
基金supported by the National Key Research Project(2020YFE0201800)Henan Province Science and Technology Program for Tackling Key Problems(21210230347)2021 Postgraduate Scientifc Re-search Innovation Progrpm of Henan Universityof Chinese Medicine(2021KYCX008).
文摘Objective Our objective was to analyze the traditional Chinese medicine(TCM)syndrome and treatment laws of diabetic kidney disease(DKD)and the action mechanism of high-frequency Chinese herbs in the treatment of DKD based on realworldstudy.MethodsThe data of patients with DKD who had been treated in the First Hospital Affiliated to Henan Universityof ChineseMedicine from January1,2014to December 31,2021 were retrospectively analyzed through the hospital information management system.The contents of the cases were statistically analyzed using IBM SPsS Statistics 25 software,and the laws of DKDtreatment were summarized.Network pharmacology and molecular docking were used to analyze the action mechanism of high-frequency Chinese herbs in the treatment of DKD.ResultsThe data of a total of 1,201 patients with DKD were included,involving 72 kinds of TCM syndromes.Nine disease nature elements and six disease location elements were extracted,involving 405 Chinese herbs.The top five high-frequency Chinese herbs were Baizhu(Atractylodis Macrocephalae Rhizoma),Fuling(Poria),Huangqi(Astragali Radix),Chuanxiong(Chuanxiong Rhizoma),and Danshen(Salviae Miltiorrhizae Radix et Rhizoma).Thirty kinds of Chinese herbs with the frequency of≥100 were mainly deficiency-tonifying herbs and blood-activating and stasis-eliminating herbs.The medicinal properties were mainly warm and mild,and the medicinal flavors were sweet and bitter mostly.For the meridian tropism,the main meridian tropism of these herbs is spleen meridian and lung meridian.The clustering method.
基金Supported by the Scientific Research Project of Shanghai Municipal Health Bureau(2008Y034)the Natural Scientific Research Project of Shanghai(05ZR14086)
文摘Objective To investigate the renoprotection effect of low molecular weight heparin(LMWH)in diabetic rats.Methods Diabetic rats were induced by injection of steptozotocin(STZ).Rats were randomly divided into three groups:control group,diabetic model group,and LMWH treatment group.The levels of total cholesterol(TC),triglyceride(TG),prothrombin time(PT),kaolin partial thromboplastin time(KPTT),24-hour urinary albumin excretion rate(UAER),and serum soluble P-selectin were determined after 8 weeks.Glomerular morphology was observed by light microscopy.Results The levels of TG,UAER,and P-selectin in LWMH treatment group were lower than those in model group(all P<0.01).The levels of PT and KPTT in LWMH treatment group were shorter than those in model group.And LWMH improved the histological changes of diabetic rats.Conclusion LMWH has some renal protective effects in diabetic rats,partly through down-regulating the expression of P-selectin.
基金ThisresearchworkwassupportedbyMinistryofPublicHealthandShanghaiBairenProjectFoundation (No .98BR0 3 8)
文摘OBJECTIVE: To investigate the effects of the mixed endothelin receptor antagonist, bosentan, combined with the long-acting calcium channel blocker, amlodipine, compared to the angiotensin-converting enzyme inhibitor, cilazapril, on the progressive renal injury in spontaneous hypertensive rats (SHR) with diabetes. METHODS: Diabetic hypertensive rats (SHR-DM) were induced by streptozotozin injected in male SHR (7-week-old),and divided into an untreated and three treated groups: 1) cilazapril treated group; 2) bosentan+amlodipine treated group; and 3) amlodipine treated group. Wistar Kyoto rats (WKY) and SHR rats served as normotensive and hypertensive control, respectively. The mean arterial blood pressure, renal function, endothelin and angiotensin II levels as well as the protein expression of renal extracellular matrix components and transforming growth factor (TGF)-beta1 were determined at the end of the 4th week. RESULTS: Mean arterial blood pressure significantly increased in SHR and SHR-DM rats compared to WKY rats. All the therapies reduced the blood pressure to normal levels. However, the enhanced urinary protein excretion, the decreased creatinine clearance as well as the increased plasma and intrarenal endothelin and angiotens in II levels were found in the untreated SHR-DM and prevented by treatment with bosentan+amlodipine and cilazapril. Similarly, these two kinds of therapies in SHR-DM abolished the overexpression of renal TGF-beta1 by Western blot analysis and reduced the accumulation of collagen type IV, laminin and fibronectin proteins by an immunochemical approach. Amlodipine monotherapy had no detectable effects on the above parameters. CONCLUSION: Bosentan combined with amlodipine can offer similar renoprotective effects on that of cilazapril and may be a potent therapy to attenuate renal injury by reducing renal protein levels of TGF-beta1 in diabetes with a hypertensive state.
文摘Nephrin is a key molecule in podocytes to maintain normal slit diaphragm structure. Nephin interacts with many other podo- cyte and slit diaphragm protein and also mediates important cell signaling pathways in podocytes. Loss of nephrin during the development leads to the congenital nephrotic syndrome in children. Reduction of nephrin expression is often observed in adult kidney diseases including diabetic nephropathy and HIV-associated nephropathy. The critical role of nephrin has been confirmed by different animal models with nepbrin knockout and knockdown. Recent studies demonstrate that knockdown of nephrin expression in adult mice aggravates the progression of' unilateral nephrectomy and Adriamycin-induced kidney disease In addition to its critical role in maintaining normal glomerular filtration unit in the kidney, nephrin is also expressed in other organs. However, the exact role of nephrin in kidney and extra-renal organs has not been well characterized. Future studies are required to determine whether nephrin could be developed as a drug target to treat patients with kidney disease.