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

To observe the effects of total flavones of Metasequoia glyptostroboides Hu et Cheng (TFM) on volume-overload cardiac hypertrophy and the expression of c-Fos protein in rat. Methods　Volume-overload cardiac hypertrophy of rat was induced by aortocaval shunts. The rats were given ig TFM (400, 40 and 4 mg/kg/d). c-Fos protein in the ventricles were measured by immunocytochemical study. Results　TFM at the above dosage decreased heart weight and contents of RNA and protein in the myocardium, inhibited the expression of c-Fos protein in the ventricles. Conclusion　TFM can prevent volume-overload cardiac hypertrophy in rats. The inhibitory effects on the expression of c-Fos protein may be its mechanism in the molecular level.

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

OBJECTIVETo investigate the genetic polymorphisms of 11 Y-chromosomal short tandem repeats (STR) loci in Chongqing Tujia population, and to evaluate their forensic application values and genetic relationships with the other 16 populations of China.

METHODSEleven Y-STR loci in 215 unrelated Tujia individuals from Chongqing were amplified with PowerPlex Y System, and the PCR products were analyzed by 310 Genetic Analyzer. Cluster analysis and phylogenic trees were applied to show the genetic distance among the populations.

RESULTSA total of 195 haplotypes were identified and the overall haplotypes diversity for the 11 Y-STR loci was 0.9942. The gene diversity values (GD) for each locus ranged from 0.3757 (DYS391) to 0.9170 (DYS385a/b). Comparing with other 16 populations, the genetic distance between Tujia and Tibetan was the nearest (0.02467), that between the Tujia and Korean ethnic groups was the farthest (0.25350).

CONCLUSIONThe genetic distribution of the 11 Y-STR loci in Chongqing Tujia population showed favorable polymorphisms. They are suitable for forensic identification and paternity testing in the local area. The study of genetic diversity among different populations is useful in understanding their origins, migrations and their relationships.

China ; ethnology ; Chromosomes, Human, Y ; Ethnic Groups ; ethnology ; genetics ; Genetic Variation ; Humans ; Male ; Microsatellite Repeats ; genetics ; Polymorphism, Genetic ; Population Groups ; genetics

Aim To observe the effect of interventional therapy of 5-fluorouracil(5-Fu), mitomycin C (MMC) and adriamycin (ADM) on solid malignant turmors in association with aterial infusion of NaHCO3.Methods Patients were randomly divided into two groups.With Seldinger technique,through the femoral atery to tumor atery.The patients in the control group were infused by anticarcinoma agents simply ,and patients in the treatment group were initially infused by NaHCO3,and then by NS 30 ml and anticarcinoma agents seperately. Results Partial remission (PR) in the group treated with NaHCO3 and anticarcinoma agents was significantly higher than in the group treated simply with anticarcinoma agents.Conclusion Aterial infusion of NaHCO3 into malignant tumors can increase the efficacy of ADM,MMC and 5-Fu.

It is reported, in the process of diabetic nephropathy (DN), inflammatory-related p38 mitogen-activated protein kinase (MAPK) signaling pathway has a close relationship with renal injury. On the one hand,many factors in the upstream including hyperglycemia, abnormal hemodynamics, oxidative stress, and pro-inflammatory cytokines could activate p38MAPK signaling pathway. On the other hand,the activated p38MAPK signaling pathway could lead to renal damage via activating inflammatory cells, inducing the expression of inflammatory mediators, and intervening cytokines production. CHM could intervene p38MAPK signaling pathway through multi-ways, including inhibiting inflammatory cytokines expression, regulating phosphorylated p38MAPK (p-p38MAPK) expression, and reducing fibrogenic factors expression.
Diabetic Nephropathies ; drug therapy ; enzymology ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Inflammation ; drug therapy ; metabolism ; Inflammation Mediators ; pharmacology ; Kidney ; drug effects ; enzymology ; metabolism ; Signal Transduction ; drug effects ; p38 Mitogen-Activated Protein Kinases ; metabolism

BACKGROUNDWith conventional imaging methods only the morphous of the visual nerve fiber bundles can be demonstrated, while the earlier period functional changes can not be demonstrated. We hypothesized that diffusion tensor imaging (DTI) would demonstrated the whole optic never fiber bundle and visual pathway and the earlier period functional changes. The purpose of the present study was to evaluate the application of DTI technique in the demonstration of the whole optic never fiber bundle and visual pathway, and the influence of orbital tumors on them.

METHODSGE 1.5 T signa HD MR System, and the software package DTV2 were adopted. The total 45 subjects were enrolled, including 15 volunteers and 30 patients. All patients had ocular proptosis from minor to major. Seven patients had visual acuity decrescence.

RESULTSThe nerve fiber bundles, e.g. optic chiasma, optic tract and optic radiation in posterior visual pathway were well demonstrated in all cases. Wherein, the intact whole visual pathway fiber bundles were clearly revealed in 10 volunteers and 17 patients, and optic nerve was not wholly revealed in the rest of the subjects. Shift of optic nerve caused by compression and partial deformation were seen in 7 patients with orbital tumor. In 6 of 7 patients, DTI displayed significant abscise and deformation of visual nerve. Chi-square test indicated significant correlation between visual acuity decrescence and DTI visual nerve non-display.

CONCLUSIONSVisual nerve fiber bundles and the whole visual pathway were visualized in most of patients with DTI. It might be an effective method of providing imaging evidence for visual nerve fiber earlier period functional changes, and laid a foundation for the study in other cranial nerves.

Adult ; Aged ; Diffusion Magnetic Resonance Imaging ; methods ; Exophthalmos ; pathology ; Female ; Humans ; Male ; Middle Aged ; Optic Chiasm ; anatomy & histology ; pathology ; Optic Nerve ; anatomy & histology ; pathology ; Visual Pathways ; anatomy & histology ; pathology ; Young Adult

Objective To investigate whether the protective effects of leonurine (SCM-198) against endotoxin induced uveitis (EIU) of SD rats caused by lipopolysaccharide (LPS) was existing,and discuss the underlying mechanisms.Methods Thirty-six normal healthy male SD rats were divided into 3 groups randomly with the same baseline bodyweight and feeding conditions.All rats received intragastric administration every day.The experimental group was devided into 4 subgroups,rats in these subgroups received SCM-198 intragastric administration by as the dose of 10,20,40 and 80 mg/kg bodyweight per day,rats in the negative control group received intragastric administration of normal saline 10 mL/kg per day,rats in the positive control group received intragastric administration ofdexamethasone (DEX) 0.5 mg/kg bodyweight per day.All rats received a 21-day-intragastric administration.The body weight of all rats was monitored every 7 days.The electroretinogram (ERG) examination was taken in the 18th day.All rats received a 100 mg S.typhi LPS intraperitoneal injection after the 21st intragastric administration.Twenty-four hours later,following anaesthesia,all rats received another ERG examination,and inflammation was scoring under microscope by 2 experienced ophthalmologists,after that the aqueous humor of all rats was collected from the left eye.The aqueous humor was kept in-80 ℃ immediately.Then the rats were sacrificed and the right eyes were immediately enucleated to finish the HE staining and immunohistochemistry (IHC) staining examination of tumor necrosis factor-α (TNF-α) and intercellular cell adhesion molecule-1 (ICAM-1).The total amount of protein in aqueous humor was detected by BCA test.Western blot was used to examine the expression of TNF-α,interleukin-1β (IL-1β),IL-6 and ICAM-1.All data was analyzed by SPSS 19.0,and differences were considered significant at P＜0.05.Results The body weight of the rats in positive control group was significantly lower (P＜0.05) than the experimental group and the negative control group after the 21-day-intragastric administration.The inflammatory score of experimental group was lower than that of the negative control group,but higher than the score of positive control group.The HE staining sections showed the similar results.The a wave of ERG in 0.01 cd of rats received 20 mg/kg SCM-198 daily intragastric administration after LPS injection was significantly lower than that before the LPS injection (P＜0.05),also lower than other groups after LPS injection.The expression of TNF-α,IL-6 and IL-1β in the aqueous humor of the rats in the subgroup of SCM-198 10 mg/kg daily intragastric administration was lower than other groups.Conclusions Intragastric administration of SCM-198 has protective effect against endotoxin induced uveitis in SD rats without obvious adverse reaction,which could alleviate the imflammatory reaction and the damage to the uvea construction.NF-κB plays an important role in the reaction.Thus,SCM-198 is a candidate potent compound with potential therapeutic applications in inflammation associated eye diseases.While the best mode and dose of administration should be further investigated.