OBJECTIVETo explore therapeutic effect and action mechanism of regulating spleen-stomach needling on diabetic nephropathy (DN).

METHODSUsing multi-centric, randomized, controlled and blind principles, 144 cases of DN were divided into an observation group and a control group according to random digital tab, 72 cases in each one. Based on regular treatment of diabetes, the regulating spleen-stomach needling was applied at Zhongwan (CV 12), Quchi (LI 11), Hegu (LI 4) and Xuehai (SP 10), etc. in the observation group while Shenshu (BL 23), Taixi (KI 3), Sanyinjiao (SP 6), Yanglingquan (GB 34), etc. were selected in the control group by reference of Acupuncture and moxibustion. The treatment was given twice a day, six days as a treatment session with interval of one day between sessions. Totally six weeks were required. Changes of clinical symptoms and signs, fast blood glucose (FBG), urinary albumin excretion rate (UAER), beta2-microglobulin (beta2-MG), monocyte chemotactic protein-1 (MCP-1), lymphocyte membrane cholesterol, propanediol (MDA), PCO, 8-hydroxydeoxy guanosine (8-OHdG), superoxide dismutase (SOD), CD3+, CD4+, CD8+, and CD4+/CD8+ were observed before and after treatment in two groups.

RESULTSAs for improving clinical symptoms and signs, total effective rate was 84.29% (59/70) in the observation group and 55.56% (40/72) in the control group, which had statistical difference between two groups (P<0.01). As for regulating glycometabolism [(6.25 +/- 0.32) mmol/L vs (8.09 +/- 0.63) mmol/L], reducing UAER [(154.43 +/- 55.14) mg/24h vs (268.91 +/- 77.65) mg/24h], restraining over-expression of MCP-1 [(137.59 +/- 36.15) pg/mL vs (166.89 +/- 42.82) pg/mL], regulating level of oxidative stress, prohibiting oxidation of protein and adjusting quantity and activity of T lymphocyte subgroup, the observation group was superior to the control group (P< 0.05, P<0.01).

CONCLUSIONThe regulating spleen-stomach needling is an effective method for treatment of DN, which cold improve glycometabolism disturbance-induced progressive kidney injury, recover glomerular filtration, reduce urinary albumin excretion rate, restrain overexpression of MCP-1, adjust level of oxidative stress, prohibit oxidation of protein, increase protectiveness of membrane, adjust quantity and activity abnormity of T lymphocyte subgroup, leading to repairing lymphocyte damage and improving immune expression to delay kidney damage.

Acupuncture Points ; Acupuncture Therapy ; Adult ; Aged ; Diabetic Nephropathies ; immunology ; physiopathology ; therapy ; Female ; Humans ; Male ; Middle Aged ; Spleen ; physiopathology ; Stomach ; physiopathology

The progression of renal damage in diabetic nephropathy(DN)is closely related to Nod-like receptor protein3(NLRP3)inflammasome activation. The characteristics of NLRP3 inflammasome activation include the changed expression and combination levels of NLRP3, apoptosis-associated speck-like protein(ASC)and pro-caspase-1, the increased expression levels of caspase-1, interleukin(IL)-1β and IL-18 and the excessive release levels of the relative inflammatory mediators. Its molecular regulative mechanisms involve the activation of multiple signaling pathways including reactive oxygen species(ROS)/thioredoxin-interacting protein(TXNIP)pathway, nuclear factor(NF)-κB pathway, nuclear factor erythroid-related factor 2(Nrf2)pathway, long non-coding RNA(lncRNA)pathway and mitogen-activated protein kinases(MAPKs)pathway. In addition, more importantly, never in mitosis aspergillus-related kinase 7(Nek7), as a kinase regulator, could target-combine with NLRP3 at upstream to activate NLRP3 inflammasome. Some extracts of Chinese herbal medicines(CHMs)such as quercetin, curcumin, cepharanthine, piperine and salidroside, as well as Chinese herbal compound prescriptions such as Wumei Pills both could treat NLRP3 inflammasome to ameliorate inflammatory renal damage in DN. Therefore, accurately clarifying the targets of anti-inflammatory CHMs and Chinese herbal compound prescriptions delaying DN progression by targeting the molecular regulative mechanisms of NLRP3 inflammasome activation will be one of the development directions in the future.
Caspase 1/immunology* ; Diabetes Mellitus/drug therapy* ; Diabetic Nephropathies/immunology* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Inflammasomes/immunology* ; Interleukin-18/immunology* ; Interleukin-1beta/immunology* ; NIMA-Related Kinases ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology*

The pathomechanisms of glomerulosclerosis in diabetic nephropathy (DN) are considered to be related with glycometabolism disorder, podocyte injury, intra-renal hemodynamics abnormality, fibrogenic cytokines over-expression, oxidative stress and inflammatory reaction. Chinese herbal medicine could delay the progression of glomerulosclerosis in DN by ameliorating the harmful factors of these pathological changes. Therefore, it is possible to postpone the progress of DN to end-stage renal disease through the treatment with Chinese herbal medicine.
Animals ; Diabetic Nephropathies ; drug therapy ; immunology ; metabolism ; prevention & control ; Drugs, Chinese Herbal ; therapeutic use ; Glomerulonephritis ; drug therapy ; immunology ; metabolism ; prevention & control ; Humans ; Oxidative Stress ; drug effects

BACKGROUNDStudies have confirmed that angiotensin II receptor blocker (ARB) and angiotensin converting enzyme inhibitors (ACEI) in the treatment of diabetic nephropathy (DN) has special advantages. We observed the effects of valsartan and metoprolol tartrate hydrchloride in treatment of DN patients with positive β1-adrenergic and anti-angiotensin II type 1 (AT1) receptor antibody.

METHODSThe epitopes of the second extracellular loop of β1 receptor (197 - 222) and AT1 receptor (165 - 191), were synthesized and used respectively to screen serum autoantibodies from patients with DN (n = 371, group A), diabetes mellitus (DM) without renal failure (n = 107, group B) and healthy blood donors (n = 47, control, group C) by enzyme-linked immunosorbent assay (ELISA). Metoprolol tartrate 25 - 50 mg, three times per day, valsartan 160 mg, once a day, aspirin 100 mg, once a day, and nitrendipine 10 - 20 mg, three times per day, were given to DN patients with positive or negative autoantibodies. The cystatin C level and 24-hour urinary protein were measured before and after treatment.

RESULTSIn DN patients, the positive rate of the autoantibodies against β1 receptors and AT1 receptor was 47.7% and 51.5%, respectively, which were significantly higher than those in DM patients and healthy controls (all P < 0.01). Patients with anormalous cystatin C had higher positive rates of the autoantibodies than patients with normal cystatin C. Valsartan and metoprolol tartrate reduced proteinuria significantly (P < 0.01) in DN patients with positive autoantibodies.

CONCLUSIONSThe findings suggest that these autoantibodies against β1 and AT1-receptor may play important roles in the pathogenesis of DN. Valsartan and metoprolol tartrate are effective and safe in the treatment of DN.

Aged ; Autoantibodies ; immunology ; Diabetic Nephropathies ; drug therapy ; immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Metoprolol ; therapeutic use ; Receptor, Angiotensin, Type 1 ; immunology ; Receptors, Adrenergic, beta-1 ; immunology ; Tetrazoles ; therapeutic use ; Valine ; analogs & derivatives ; therapeutic use ; Valsartan

OBJECTIVETo investigate the role of CD4+CD25+Foxp3+ regulatory T cells (Treg) in type 2 diabetic nephropathy and provide new clues for prevention and treatment of type 2 diabetic nephropathy.

METHODSFlow cytometry was used to analyze the expression rate of CD4+CD25+Foxp3+ Treg cells in 60 patients with type 2 diabetes and 15 normal subjects.

RESULTSNo significant difference was found in the expression rate of CD4+CD25+Foxp3+ Treg cells between the control group and the type 2 diabetic patients. In the type 2 diabetic patients with microalbuminuria and macroalbuminuria, the expression of CD4+CD25+Foxp3+ Treg cells was significantly lowered in comparison with that in the control group (P<0.05), and patients with macroalbuminuria showed significantly lower expression of CD4+CD25+Foxp3+ Treg cells than the microalbuminuric patinets (P<0.05). Significant inverse correlations were noted between the disease course and the expression of CD4+CD25+Foxp3+ Treg cells and between the urinary albumin excretion rate (UAER) and the expression of CD4+CD25+Foxp3+ Treg cells.

CONCLUSIONCD4+CD25+Foxp3+ Treg cells may play a role in the occurrence and development of type 2 diabetic nephropathy.

Adult ; Aged ; CD4 Antigens ; immunology ; metabolism ; Case-Control Studies ; Diabetes Mellitus, Type 2 ; immunology ; Diabetic Nephropathies ; immunology ; Female ; Flow Cytometry ; Forkhead Transcription Factors ; immunology ; Humans ; Interleukin-2 Receptor alpha Subunit ; immunology ; metabolism ; Male ; Middle Aged ; T-Lymphocyte Subsets ; immunology ; T-Lymphocytes, Regulatory ; immunology ; metabolism

OBJECTIVETo explore methods of preventing and reversing rejection after simultaneous pancreas-kidney transplantation (SPK).

METHODSSeventeen patients performed SPK operation from Sep, 1999 to Sep, 2003 were reviewed retrospectively. Immunosuppression was achieved by triple regimen consisting of cyclosporine, mycophenolate mofetil (MMF)/azathioprine and steroid. 2 patients were treated with Dalizumab, the other three patients used OKT3 as immune induction.

RESULTS1 patient experienced the accelerated rejection, the pancreas and kidney grafts were resected because of failure of conservative therapy. 8 patients experienced renal acute rejection, 2 cases suffered from pancreas acute rejection at the same time. All these patients received daily high dose pulse steroid for 3 days. OKT3 was administered in 2 patients with steroid resistance rejection. All the grafts were successfully rescued.

CONCLUSIONSReasonable application of immunosuppression after SPK operation and adoption of systemic measures which can reduce sensitivity of high risk receptor before SPK operation are the effective methods of preventing and treating rejection.

Administration, Oral ; Adult ; Azathioprine ; administration & dosage ; Cyclosporine ; administration & dosage ; Diabetic Nephropathies ; surgery ; Drug Therapy, Combination ; Female ; Glucocorticoids ; administration & dosage ; Graft Rejection ; prevention & control ; Humans ; Immunosuppressive Agents ; administration & dosage ; Kidney Transplantation ; immunology ; Male ; Middle Aged ; Pancreas Transplantation ; immunology ; Prednisolone ; administration & dosage ; Retrospective Studies ; Transplantation, Homologous

OBJECTIVETo study the effect of Astragalus mongholicus on renal gene expression profile in mice with diabetic nephropathy by cDNA microarray.

METHODThe mice with diabetic nephropathy were fed A. mongholicus and normal saline respectively. cDNA microarray was used to measure gene expression profile in renal tissue after 12 weeks, and the data were analyzed by bioinformatics. RT-PCR was performed to detect the relative levels of some genes which were randomly selected.

RESULTEighty eight genes were found differently expressed in two chips. Among these genes, 81 genes were found differently expressed in reverse direction change, 7 genes were found differently expressed in same direction change. The genes altered were mainly related to material metabolism, immunity and inflammatory reaction, signal transduction, translation, transcription, et al. The expressions of genes tested by RT-PCR were in accordance with those detected by cDNA microarray.

CONCLUSIONA. mongholicus may play protective roles in diabetic nephropathy through multiple pathways at gene level. The effect of A. mongholicus in genes related to material metabolism is more significant.

Animals ; Astragalus Plant ; chemistry ; Blood Glucose ; metabolism ; Diabetic Nephropathies ; drug therapy ; genetics ; immunology ; pathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Gene Expression Profiling ; Gene Expression Regulation ; drug effects ; Inflammation ; drug therapy ; Kidney ; drug effects ; metabolism ; pathology ; Male ; Mice ; Oligonucleotide Array Sequence Analysis ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; drug effects