Along with the development of clinical and pathological studies, and the wide spreading of the concepts or ideas of chronic kidney disease (CKD) and diabetic kidney disease (DKD), the clinical research of DKD has entered a new stage, which has brought new requirements for Chinese medicine treatment of DKD. It is necessary to carry out good design, have reasonable inclusion and exclusion criteria, select appropriate biomarkers capable of reflecting the pathophysiology of DKD, choose convincible hard endpoints capable of reflecting the prognosis of DKD, and conduct observations of enough long therapeutic course. This is the main trend of conducting clinical trials of DKD and scientifically assessing the efficacy of Chinese medicine treatment of DKD.
Diabetic Nephropathies ; diagnosis ; drug therapy ; pathology ; Humans ; Medicine, Chinese Traditional ; trends

Diabetic kidney disease (DKD) is the primary cause of mortality among diabetic patients. With the increasing prevalence of diabetes, it has become a major concern around the world. The therapeutic effect of clinical use of drugs is far from expected, and therapy choices to slow the progression of DKD remain restricted. Therefore, research on new drugs and treatments for DKD has been a hot topic in the medical field. It has been found that rhein has the potential to target the pathogenesis of DKD and has a wide range of pharmacological effects on DKD, such as anti-nephritis, decreasing blood glucose, controlling blood lipids and renal protection. In recent years, the medical value of rhein in the treatment of diabetes, DKD and renal disease has gradually attracted worldwide attention, especially its potential in the treatment of DKD. Currently, DKD can only be treated with medications from a single symptom and are accompanied by adverse effects, while rhein improves DKD with a multi-pathway and multi-target approach. Therefore, this paper reviews the therapeutic effects of rhein on DKD, and proposes solutions to the limitations of rhein itself, in order to provide valuable references for the clinical application of rhein in DKD and the development of new drugs.
Humans ; Diabetic Nephropathies/drug therapy* ; Kidney/pathology* ; Anthraquinones/therapeutic use* ; Diabetes Mellitus

PURPOSE: Oxidative stress has been suggested to play a role as a common mediator of apoptosis and kidney damage in diabetes. However, it is uncertain whether the apoptosis occurs in the kidney during the course of diabetes. We investigated the occurrence of apoptosis in the diabetic rat kidney, the role of oxidative stress and the effect of an antioxidant on apoptosis in the diabetic rat kidney. MATERIALS AND METHODS: Otsuka-Long-Evans-Tokushima-Fatty rats, an animal model for type 2 diabetes, were randomized into a non-treated diabetic (n=8) and a vitamin C-treated group (n=8). Long-Evans Tokushima Otsuka rats (n=8) were used as a control. RESULTS: Apoptosis was present in the epithelial cells of the proximal tubules in diabetic rats. The number of apoptotic cells, albuminuria, proteinuria, glomerular and tubulointerstitial sclerosis, and renal malondialdehyde were significantly decreased in vitamin C-treated diabetic rats when compared to the untreated diabetic rats. The decreased slit pore density (number of slit pores per underlying glomerular basement membrane length) as assessed by electron microscopy was also significantly restored by treatment with vitamin C without significantly affecting plasma glucose in diabetic rats. CONCLUSION: By blocking these pathophysiologic processes, a blockade of oxidative stress by vitamin C might become a useful adjunct to albuminuria and renal sclerosis in diabetic nephropathy.
Albuminuria/*drug therapy ; Animals ; Antioxidants/*therapeutic use ; Apoptosis/drug effects ; Ascorbic Acid/*therapeutic use ; Diabetes Mellitus, Experimental/*drug therapy/pathology ; Diabetic Nephropathies/*drug therapy/pathology ; Kidney/*pathology ; Male ; Oxidative Stress/*drug effects ; Rats ; Rats, Inbred OLETF ; Sclerosis

Glomerular hypertrophy is the main pathological characteristic in the early stage of diabetic nephropathy (DN), and its regulatory mechanism is closely related to mammalian target of rapamycin (mTOR) signaling pathway activity. mTOR includes mTOR complex 1 (mTORC1) and mTOR complex 2(mTORC2), in which, the upstream pathway of mTORC1 is phosphatidylinositol-3-kinase (PI3K)/serine-threonine kinase(Akt)/adenosine monophosphate activated protein kinase(AMPK), and the representative signaling molecules in the downstream pathway of mTORC1 are 4E-binding proteins(4EBP) and phosphoprotein 70 S6Kinase(p70S6K). Some Chinese herbal extracts could improve cell proliferation via intervening the expressions of the key molecules in the upstream or downstream of PIK/Akt/mTOR signaling pathway in vivo. As for glomerular mesangial cells(MC) and podocyte, mTOR plays an important role in regulating glomerular inherent cells, including adjusting cell cycle, energy metabolism and matrix protein synthesis. Rapamycin, the inhibitor of mTOR, could suppress glomerular inherent cell hypertrophy, cell proliferation, glomerular basement membrane (GBM) thickening and mesangial matrix deposition in model rats with DN. Some Chinese herbal extracts could alleviate glomerular lesions by intervening mTOR signaling pathway activity in renal tissue of DN animal models or in renal inherent cells in vivo and in vitro.
Animals ; Diabetic Nephropathies ; drug therapy ; enzymology ; genetics ; pathology ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Hypertrophy ; drug therapy ; enzymology ; genetics ; pathology ; Kidney Glomerulus ; drug effects ; metabolism ; pathology ; Signal Transduction ; drug effects ; TOR Serine-Threonine Kinases ; genetics ; metabolism

This study aimed to investigate the therapeutical effects of Rhodiola rosea extract on rats with type 2 diabetic nephropathy (DN). The rat type 2 DN model was established by high fat and high calorie feeding and intravenous injection of streptozocin (STZ). Wistar rats were randomly divided into normal group, control group, low dose Rhodiola rosea group, high dose Rhodiola rosea group and Captopril group. Oral glucose tolerance test (OGTT) was performed to determine the impairment of glucose tolerance in the established animal model. A series of parameters including fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), creatinine clearance rate (Ccr), 24-h urinary albumin (UA), the ratio of kidney mass/body weight (renal index) and glomerular area were examined after 8 weeks. Moreover, the expression of transforming growth factor (TGF)-β1 in renal tissues was detected by using immunohistochemisty. At the end of the eighth week, FBG, TC, TG, Ccr, 24-h urinary albumin, the ratio of kidney mass/body weight and glomerular area were significantly reduced in Rhodiola rosea extract treatment groups as compared with those in control group. TGF-β1 expression in renal tissues of Rhodiola rosea extract treatment groups was also significantly decreased as compared with that of control group. These results indicate that Rhodiola rosea extract may have a protective effect on early nephropathy in diabetic rats, which might be related to the decrease of the renal expression of TGF-β1.
Animals ; Diabetes Mellitus, Type 2 ; drug therapy ; pathology ; physiopathology ; Diabetic Nephropathies ; drug therapy ; pathology ; physiopathology ; Drugs, Chinese Herbal ; administration & dosage ; Ethanol ; chemistry ; Glomerular Filtration Rate ; drug effects ; Male ; Plant Extracts ; administration & dosage ; chemistry ; Rats ; Rats, Wistar ; Rhodiola ; chemistry ; Treatment Outcome

OBJECTIVETo investigate the morphological changes and expressions of desmin and podocin in podocytes of rats with diabetic nephropathy (DN) rats and renal protection mechanism of Shenkangwan.

METHODSDN model was established in rats by a single injection of streptozotocin. The rats were then randomly divided into model group, Shenkangwan treatment group, irbesartan treatment group, and Shenkangwan plus irbesartan treatment group, with normal rats as the control group. All the rats received daily gavage for 8 weeks. The urinary protein quantity in 24 h were detected, and the morphological changes of the kidneys were observed with optic and transmission electron microscopes. The expressions of desmin and podocin in the podocytes were detected by immunohistochemistry.

RESULTSShenkangwan and irbesartan reduced the urinary protein quantity in 24 h and alleviated the renal damage in DN rats, and the expression of desmin was significantly attenuated while podocin expression increased in the podocytes.

CONCLUSIONSShenkangwan can provide renal protection against DN in rats and alleviate the structural and functional damages of podocytes possibly by reducing desmin expression and increasing podocin expression in the podocytes.

Animals ; Desmin ; biosynthesis ; Diabetic Nephropathies ; drug therapy ; pathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Immunohistochemistry ; Kidney ; drug effects ; pathology ; ultrastructure ; Male ; Microscopy, Electron, Transmission ; Phytotherapy ; Podocytes ; drug effects ; metabolism ; pathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate nephrin and desmin expression in rat podocytes in early diabetic nephropathy (DN) and the rale of angiotensin II receptor antagonist in renal protection.

METHODSRat models of DN established by a injection of a single dose of streptozotocin (STZ) were randomized into model group and irbesartan group, with rats without STZ injection as the normal control group. The rats in irbesartan group were subjected to daily intragastric irbesartan administration for 8 consecutive weeks, while those in the model group received only saline in the same manner. Upon completion of the treatment, the rats were sacrificed and pathological changes of the kidney were examined with optical and transmission electron microscope. Nephrin and desmin expressions in the podocytes were detected by immunohistochemistry.

RESULTSIn rats with DN, irbesartan administration alleviated podocyte injury and significantly lowered the expression of nephrin and desmin (P<0.05).

CONCLUSIONAngiotensin II receptor antagonist may offer renal protection against DN by alleviating structural and functional podocyte damage through decreasing nephrin expression in the podocytes.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Animals ; Biphenyl Compounds ; therapeutic use ; Desmin ; metabolism ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetic Nephropathies ; drug therapy ; Kidney ; pathology ; Membrane Proteins ; metabolism ; Podocytes ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Tetrazoles ; therapeutic use

OBJECTIVETo investigate the renal protective activity of Hsian-tsao Mesona procumbens Hemsl. water extracts in diabetic rats.

METHODSThirty Sprague-dawley female rats were randomly divided into three groups (n = 10 each), "control group" with intraperitoneal saline injection, "diabetic group" with 60 mg of intraperitoneal streptozotocin injection per kg of body weight and "Hsian-tsao group" with intragastric administration of Hsian-tsao extraction everyday for 4 weeks after intraperitoneal streptozotocin injection. The body weight and blood sugar were measured before and after model induction in the three groups. Thrombospondin-1 (TSP-1) expressions in the kidney were monitored by immunohistochemistry. Kidney ultrastructural changes were also analyzed by using transmission electron microscopy.

RESULTSBefore diabetic model induction, there were no significant differences among the three groups in body weight and blood sugar. Four weeks after the induction of diabetes, the differences became statistically significant. Electron microscopy also revealed disruption of the foot processes of the podocytes and other damages in diabetic group. These damages were significantly less severe in Hsian-tsao group when compared with the diabetic group. TSP-1 expressions in the kidney were significantly increased in both the diabetic group and Hsian-tsao group, but it was relatively lower in Hsian-tsao group than in diabetic group.

CONCLUSIONOur results showed that Hsian-tsao treatment in the diabetic rats effectively prevented the pathological alterations in the kidney and decreased the TSP-1 expression. It was suggested that Hsian-tsao had protective effect on the kidneys of the diabetic rats.

Animals ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; pathology ; Diabetic Nephropathies ; metabolism ; pathology ; prevention & control ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Kidney ; drug effects ; metabolism ; pathology ; ultrastructure ; Lamiaceae ; chemistry ; Rats ; Rats, Sprague-Dawley ; Thrombospondin 1 ; metabolism

OBJECTIVETo study the protective effects of naja naja atra venom (NNAV) in a rat model of diabetic nephropathy (DN).

METHODSThe rat diabetes model was induced by intraperitoneal injection of streptozotocin (STZ). Thirty-two model rats were randomly divided into one DN group (n=8) and three treatment groups (n=8 each) that received NNAV at doses of 30, 90, or 270 μg/(kg·day) via oral gavage, another eight rats as normal controls. After 12 weeks, all rats were sacrificed and the changes in serum and urine biological index levels were determined by colorimetric assay. Microalbumin (mALB), N-acetyl-β- glucosaminidase (NAG) and cystatin C (CysC) concentrations were measured by ELISA. Renal tissues were sliced for pathological and immunohistochemical observations.

RESULTSComparied with the DN group, serum glucose was decreased by 31.04%, total cholesterol 21.96%, triglyceride 23.78%, serum creatinine 19.83%, blood urea nitrogen 31.28%, urinary protein excretion 45.42%, mALB 10.42%, NAG 20.65%, CysC 19.57%, whereas albumin increased by 5.55%, high-density lipoprotein-cholesterol 59.09%, creatinine clearance 19.05% in the treatment group by NNAV administration at dose of 90 μg/(kg·day). NNAV also reduced the levels of malondialdehyde in serum (22.56%) and kidney tissue (9.79%), and increased superoxide dismutase concentration in serum (15%) and decreased it in renal tissue (8.85%). In addition, under light microscopy kidney structure was improved and glomerular hypertrophy decreased by 8.29%. As shown by immunohistochemistry, NNAV inhibited transforming growth factor-β1 by 6.70% and nuclear actor-κB by 5.15%.

CONCLUSIONNNAV improves biological indexes in DN, and it may exert renoprotective effects in rats with STZ-induced diabetes.

Animals ; Body Weight ; Diabetes Mellitus, Experimental ; complications ; Diabetic Nephropathies ; drug therapy ; pathology ; Dose-Response Relationship, Drug ; Elapid Venoms ; administration & dosage ; pharmacology ; Elapidae ; physiology ; Kidney ; drug effects ; pathology ; Male ; Malondialdehyde ; Organ Size ; Rats ; Rats, Wistar ; Superoxide Dismutase

OBJECTIVETo study the mechanism of Shenkangwan (SKW) in treating early diabetic nephropathy (DN).

METHODSThe effect of SKW on NO and transforming growth factor (TGF)-beta(1) production by the mesangial cells (MCs) of rats with early diabetic nephropathy was evaluated with serum pharmacological method.

RESULTSCompared with normal serum, the SKW-containing serum dose- and time-dependently inhibited TGF-beta(1) excretion and increased NO production in the MCs of rats with early DN (P<0.05 and P<0.01, respectively).

CONCLUSIONThe therapeutic effect of SKW on early DN may rely on the balance modulation of cytokine network by increasing NO production and decreasing TGF-beta(1) excretion to prevent cytokine-induced damage of the MCs.

Animals ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; Diabetic Nephropathies ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Glomerular Mesangium ; metabolism ; pathology ; Male ; Nitric Oxide ; biosynthesis ; Rats ; Rats, Wistar ; Transforming Growth Factor beta ; biosynthesis