Animal models with kidney disease are generally divided into two types. One belongs to the models which imitate human kidney disease by the artificial operations, such as anti-glomerular basement membrane antibody nephritis, Heymann nephritis, anti-Thyl. 1 antibody nephritis, BSA nephritis and puromycin nephropathy. The other one pertains to the models which make themselves kidney disease, and appear the pathological characteristics naturally as like as human, such as HIGA mice with IgA nephropathy and NZB/WF1 and MRL/1pr mice with lupus nephritis. In addition,the transgenic animal models with kidney disease can also be established by the modern molecular biologic techniques including gene knockout and siRNA transfection. As for the studies related with kidney disease in pharmacodynamics and pharmacology of Chinese herbal medicine (CHM), it is important to understand deeply the features of each animal model with kidney disease, and select accurately the proper models according to the different experimental objectives, and then, build the special models provided with the combination of disease with syndrome in traditional Chinese medicine (TCM). Therefore,it is the developmental direction for the further study to establish animal models with kidney disease, which should possess the characteristics of syndrome in TCM.
Animals ; Diabetic Nephropathies ; etiology ; Disease Models, Animal ; Humans ; Kidney Diseases ; etiology ; Medicine, Chinese Traditional ; Mice ; Streptozocin

Objective To study the expression and change of neuropeptide substance P (SP) during the wound healing of deep partial thickness scalding in diabetic rats. Methods Eighty-four Wistar rats were randomly divided into diabetes mellitus group (n=42) and control group (n=42). Diabetic rat models were established by intraperitoneal injection of streptozotocin (STZ) in diabetes mellitus group, and those in control group were intraperitoneally injected with aseptic citrate buffer solution. Deep partial thickness scalding with diameter of 2 cm on the back were prepared in all the rats. The pre-scalding and post-scalding wound specimens of different time points were obtained, and the percentages of wound closure were calculated. The wound specimens were also obtained for immunohistological staining to compare the areas with positive staining of SP, and ELISA was employed to detect the expression of SP in the wound tissues. Results The percentage of wound closure was significantly lower in diabetes mellitus group than that in control group from 7 days post-scalding (P< 0.01). The areas with positive staining of SP in diabetes mellitus group were much smaller than those in control group at different time points, which was most significant on the seventh day post-scalding[(1 350.93±99.28) μm2 vs(1 715.86± 103.41) μm2](P < 0.01). The expression of SP in the wound tissues was significantly lower in diabetes mellitus group than that in control group at different time points, which was most significant on the seventh day post-scalding[(114.04±9.96) vs(143.39±8.94)](P<0.01). Conclusion The significantly lower expression of SP in wound site may be one of the causes of delayed wound healing in diabetic rats.

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

OBJECTIVETo demonstrate the effects and mechanisms of Huangkui capsule (HKC) on renal fibrosis in rats with diabetic nephropathy (DN).

METHODRats were randomly divided into 5 groups, the sham-operated group (Sham group, n = 5), the vehicle-given group (Vehicle group, n = 7), the low dose of HKC-treated group (L-HKC group, n = 7), the high dose of HKC-treated group (H-HKC group, n = 7) and the lipoic acid (LA)-treated group (LA group, n = 7). DN models were induced by intraperitoneal injection of streptozotocin (STZ,35 mg x kg(-1)) twice and unilateral nephrectomy. After models were successfully established, the rats in HKC and LA groups were daily administrated with HKC suspensions (0.75, 2 g x kg(-1)) or LA suspensions (60 mg x kg(-1)) respectively, and at the same time, the rats in Vehicle group were daily administrated with distilled water (2 mL) for 8 weeks. All rats were sacrificed at the end of week 8 to collect blood and renal tissues. UAlb, renal function, renal fibrotic morphologic characteristics, as well as oxidative stress (OS)-related markers, the protein expressions of the key signaling molecules in p38 mitogen-activated protein kinase (p38MAPK) signaling pathway, fibrogenic cytokines and inflammatory factors were examined respectively.

RESULTHKC, similar to LA, improved the general state of health, body weight, UAlb, BUN, UA and Alb in DN model rats. Of note, renal fibrosis was ameliorated in HKC groups,especially in H-HKC group which was better than that in LA group. In addition, HKC not only improved the main indexes of OS in the kidney like LA, but also down-regulated the protein expressions of phosphorylated-p38MAPK (p-p38MAPK), transforming growth factor (TGF)-β1 and tumor necrosis factor(TNF)-α in the kidney, whereas, LA only decreased the protein expression of TNF-α in the kidney in DN model rats.

CONCLUSIONHKC, similar to LA, has the actions of anti-OS in vivo. Moreover, HKC could attenuate renal fibrosis by suppressing the activation of p38MAPK signaling pathway and the protein expressions of fibrogenic cytokines and inflammatory factors in the kidney in DN model rats, which is different from LA.

Abelmoschus ; chemistry ; Animals ; Capsules ; Diabetic Nephropathies ; drug therapy ; metabolism ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Fibrosis ; Kidney ; drug effects ; pathology ; MAP Kinase Signaling System ; drug effects ; Male ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley ; p38 Mitogen-Activated Protein Kinases ; antagonists & inhibitors

OBJECTIVETo explore the effects and mechanisms of multi-glycoside of Tripterygium wilfordii (GTW) on improving glomerular inflammatory lesion in rats with diabetic nephropathy (DN).

METHODDN model was induced by unilateral nephrectomy and intraperitoneal injection of STZ (35 mg x kg(-1)) twice. The rats were randomly divided into 3 groups, the sham-operated group (Sham group, n = 5), the vehicle-given group (Vehicle group, n = 5 ) and GTW-treated group (GTW group, n = 5). After the model was successfully established, the rats in GTW group were daily oral administrated with GTW suspension (50 mg x kg(-1) x d(-1)), meanwhile, the rats in Vehicle group were daily oral administrated with distilled water (2 mL) for 8 weeks. From the beginning of the administration, all rats were killed 8 weeks later. Blood and renal tissues were collected,and then UAlb, renal function, glomerular morphology characteristics and glomerular macrophages (ED1 + cells) infiltration, as well as the protein expressions of inflammatory cytokines including tumor necrosis factor(TNF)-α and interleukin(IL)-lβ, and the key molecules in p38MAPK signaling pathway including p38 mitogenactivated protein kinase (MAPK), phosphorylated p38 (p-p38MAPK) and transforming growth factor(TGF)-β1 were investigated respectively.

RESULTGTW not only ameliorated the general state of health and body weight,but also attenuated UAlb, glomerulosclerosis, the infiltration of glomerular ED1 + cells and the protein expressions of TNF-α, IL-1β, p-p38MAPK and TGF-β1 in the kidney in DN model rats.

CONCLUSIONBy means of DN model rats, we demonstrated that GTW has the protective effect on renal inflammatory damage in vivo via inhibiting inflammatory cells infiltration and inflammatory cytokines expression. Furthermore, GTW could improve renal inflammatory lesion through down-regulating the expressions of the key signaling molecules in p38MAPK pathway such as p-p38MAPK and TGF-β1 ,and inhibiting the activation of p38MAPK signaling in the kidney.

Animals ; Diabetic Nephropathies ; drug therapy ; Disease Models, Animal ; Glomerulonephritis ; drug therapy ; Glycosides ; pharmacology ; MAP Kinase Signaling System ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; analysis ; Tripterygium ; chemistry ; p38 Mitogen-Activated Protein Kinases ; physiology

In the development of diabetic nephropathy (DN), reactive oxygen specie (ROS) over much in vivo leads to oxidative stress(OS)-related renal injuries, which are characterized by the structural and functional changes in glomerular and renal tubular cells in morphology. The regulative approaches of OS involve the several signaling pathways, in which, both p38 mitogen-activated protein kinase (MAPK) signaling pathway and adenosine monophosphate-activated protein kinase (AMPK) signaling pathway play the important roles as the target of anti-oxidants. The interventional actions of Chinese herbal compound prescriptions and the extracts of single Chinese herbal medicine (CHM) on OS in the kidney in DN include regulating the balance between ROS and antioxidants, reducing the production of AGEs, inhibiting the expression of growth factors and intervening the activity of signaling pathways.
Animals ; Diabetic Nephropathies ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Kidney ; drug effects ; metabolism ; Oxidative Stress ; drug effects ; Signal Transduction ; drug effects ; Treatment Outcome

The identity of higher-order neurons and circuits playing an associative role to control renal function is notwell understood.We identified specific neural populations of rostral elements of brain regions that project multisynaptically to the kidneys in 3~ days after injecting a retrograde tracer pseudorabies virus (PRV)-614 into kidney of 13 adult male C57BL/6J strain mice.PRV-614 infected neurons were detected in a number of mesencephalic (e.g.central amygdala nucleus),telencephalic regions and motor cortex.These divisions included the preoptic area (POA),dorsomedial hypothalamus (DMH),lateral hypothalamus,arcuate nucleus (Arc),suprachiasmatic nucleus (SCN),periventricular hypothalamus (PeH),and rostral and caudal subdivision of the paraventricular nucleus of the hypothalamus (PVN).PRV-614/Tyrosine hydroxylase (TH) double-labeled cells were found within DMH,Arc,SCN,PeH,PVN,the anterodorsal and medial POA.A subset of neurons in PVN that participated in regulating sympathetic outflow to kidney was catecholaminergic or serotonergic.PRV-614 infected neurons within the PVN also contained arginine vasopressin or oxytocin.These data demonstrate the rostral elements of brain innervate the kidney by the neuroanatomical circuitry.

OBJECTIVETo investigate and discuss the diagnosis and treatment of ectopic ACTH syndrome.

METHODSClinical data of 32 cases of ectopic ACTH syndrome, recruited from January 1990 to April 2003 in our hospital, was analyzed.

RESULTSAll of the 32 cases presented with clinical and biochemical evidences of Cushing's syndrome. Ten cases were definitively diagnosed as ectopic ACTH syndrome by finding ectopic tumors; 4 cases were highly suspected as ectopic ACTH by blood sampling from femoral vein and infra-petrosal vein and 18 cases were suspected as ectopic ACTH by imaging examinations. Fifteen cases (47%), without identified source of ectopic hormone, were treated with bilateral or unilateral total adrenalectomy, with 1-year survival rate of 60%. Seven cases (22%), with possible source of ectopic hormone, underwent no intervention, with 1-year survival rate of 0. Ten cases underwent radical resection of tumor, 6 of which were bronchial carcinoids and 4 of which were thymic carcinoids, with 1-year survival rate of 60%.

CONCLUSIONIt is very difficult to localize the tumor of ectopic ACTH syndrome patients. Bilateral adrenalectomy followed by hormonal replacement is effective for most of the patients without identifying source of ectopic hormone.

ACTH Syndrome, Ectopic ; diagnosis ; mortality ; therapy ; Adolescent ; Adrenalectomy ; methods ; Adult ; Aged ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Survival Rate

OBJECTIVEFor heart functional parameters, we commonly used normal range. The reference values and predict formulas of heart functional parameters and their relationships with individual characteristics are still lack.

METHODSLeft ventricular (LV) volumes (end-diastolic volume and end-systolic volume), stroke volume (SV), ejection fraction (EF) and cardiac output (CO) were measured by cardiac CT angiography (CAT) in 1 200 healthy Caucasian volunteers, men 807 and women 393, and age 20-90yr. The results are analyzed by high-accuracy three-dimensional imaging technology, and then measured the dynamic changes of the volumes of each atriam and ventricule during their contractions and relaxations. The gender, age, height and weight were analyzed by multiple linear regression to predict LV functional parameters.

RESULTSExcept the LVEF was lower in man than in women (P < 0.001), all other LV functional parameters of EDV, ESV, SV, FE and CO were higher in man (P < 0.001). Multiple linear regression indicated that age, gender, height and weight are all independent factors of EDV, ESV and SV (P < 0.001). CO could be significantly predicted by age, gender and weight (P < 0.001), but not height (P > 0.05). The predict equation for CO (L x min(-1)) = 6.963+0.446 (Male) -0.037 x age (yr) +0.013 x weight (kg).

CONCLUSIONAge, gender, height and weight are predictors of heart functions. The reference values and predict equations are important for noninvasive and accurate evaluation of cardiovascular disease and individualized treatment.

Adult ; Age Factors ; Aged ; Aged, 80 and over ; Body Height ; Body Weight ; Cardiac Output ; Female ; Heart ; physiology ; Humans ; Male ; Middle Aged ; Reference Values ; Sex Factors ; Stroke Volume ; Ventricular Function, Left ; Young Adult

BACKGROUNDAutologous transplantation of the submandibular gland (SMG) into the temporal fossa with microvascular anastomosis has been successfully applied in severe xerophthalmia patients as a permanent tear substitute. However, severe xerophthalmia can be accompanied by salivary gland dysfunction, making such autotransplantation unsuitable. Therefore, SMG allotransplantation might be a solution. The aim of this study was to assess the technical feasibility of submandibular gland allotransplantation.

METHODSTwelve miniature swine were randomized to serve as donors or recipients. One SMG was transplanted between a donor and a recipient. The donor SMG was revascularized by microvascular anastomosis of its vascular pedicle to the recipient lingual artery and external jugular vein. The secretory duct was implanted into the vestibule of the mouth through a subcutaneous tunnel. No immunosuppressive agent was administered. The results were assessed by visual inspection of the secretion, and histopathological examination of the transplanted SMG.

RESULTSTechnically, all surgical procedures were successful. Clear secretion flowed out of the duct as soon as blood supply of the transplanted submandibular gland was reestablished. The secretion of the gland lasted for 5 days. As expected, an acute rejection reaction occurred after surgery because no immunosuppressive agents were used. Secretion from the transplanted SMG ceased within 5 days.

CONCLUSIONSA model of SMG allotransplantation can be established in miniature swine. The technique of submandibular gland allotransplantation is feasible.

Animals ; Microscopy, Electron ; Models, Animal ; Submandibular Gland ; pathology ; transplantation ; ultrastructure ; Swine ; Swine, Miniature ; Transplantation, Homologous