Objective To evaluate the regulatory role of mTOR signaling in activation of renal interstitial fibroblasts and the potential effect on interstitial fibrosis. Methods 8-week old female C57BL/6 mice (n=30) underwent unilateral ureteral obstruction (UUO) to induce renal interstitial fibrosis. Animals were randomly divided into rapamycin (2 mg·kg-1· d-1) group and UUO group (vehicle-treated) (n=15 each group). Daily intraperitoneal injection of rapamycin or saline was applied to animals from day 1 before operation to the end of experiment.Three mice were sacrificed at day 1,3,7,14 respectively and kidneys were harvested for further analysis.NIH3T3 cells were stimulated by TGF-β for 12 hours with the presence or bsence of rapamycin (100 nmol/L). Results Immunofluorescent co-staining revealed that active fibroblasts highly expressed pS6K and α-SMA in kidney interstitium.Administation of rapamycin significantly inhibited activation of mTOR signaling in fibroblasts and ameliorated interstitial fibrosis of obstructed kidneys.Real-time PCR confirmed that rapamycin decreased the mRNA expression of FSP1,TGF-β,CTGF and Col4A1 in fibrotic kidneys. In vitro experiment revealed that TGF-β induced highly expression of pS6K and αSMA in cultured NIH3T3 cells,which could be markedly inhibited by rapamycin. Conclusions mTOR signaling highly activates in interstitial fibroblasts during kidney fibrosis.Inhibition of mTOR signaling by rapamycin decreases the activation of fibroblasts and ameliorates interstitial fibrosis.

Apoproteins ; analysis ; Epithelium ; chemistry ; ultrastructure ; Humans ; Lung ; chemistry ; pathology ; Nuclear Proteins ; analysis ; Pulmonary Sclerosing Hemangioma ; chemistry ; pathology ; Pulmonary Surfactant-Associated Proteins ; analysis ; Secretory Component ; analysis ; Thyroid Nuclear Factor 1 ; Transcription Factors ; analysis

Objective To evaluate the effect of prefilling blood reservoir with mannitol-adeninephosphate MAP) solution on the damage to erythrocytes in intraoperative salvaged blood in patients.Methods One hundred and fifty blood samples were collected from 150 patients who were scheduled for elective spinal surgery requiring blood salvage,and were equally and randomly divided into 5 groups (n =30 each) using a random number table:group N,group N1,group N2,group M1 and group M2.The blood reservoir was not prefilled before surgery in group N,while the blood reservoirs in N1,N2,M1 and M2 groups were prefilled with normal saline (NS) 100 ml,NS 200 ml,MAP solution 100 ml and MAP solution 200 ml,respectively.Blood sauples were obtained for erythrocyte osmotic fragility test after the salvaged blood was washed,and hemolysis rates in different concentrations of hypotonic NaCl solution were calculated.The concentration of free hemoglobin in the clear supernatant liquid (FHb) of washed blood placed for 0 h (T0),1 h (T1) and 2 h (T2) were detected.Results Compared with N and N1 groups,the hemolysis rate of washed erythrocytes under 0.48％ 0.68％ NaCl solutions was significantly decreased,the concentration of FHb at T1 was decreased,and no significant change was found in FHb at T2 in group M1.Compared with N and N2 groups,the haemolysis rates of washed erythrocytes under 0.48％-0.68％ NaCl solutions were significantly decreased,and the concentrations of FHb at T1,2 were decreased in group M2.The concentration of FHb was significantly lower at T2 in group M2 than in group M1.Conclusion Prefilling blood reservoir with MAP solution can mitigate the damage to erythrocytes in the intraoperative salvaged blood in patients,and the efficacy of prefilling of 200 ml is superior to that of prefilling of 100 ml.

0.05).Amplitudes of OPs and b wave were significantly decreased after experiment in STZinduced diabetic group(P

Objective To define the effect and mechanism of hyperkalemic solution on atrial natriuretic peptide (ANP) secretion in rabbits. Methods Eighteen rabbits were selected and the chest was opened under anes-thetization to remove the heart. The left atrium was isolated and fixed in the atrial perfusion system with proper electric stimulation for beating. The following experiments were carried out on beating rabbit atria: ①The atrium was perfused for 60 min to stabilize parameters of ANP secretion and atrial dynamics. The control period (12 min as an experimental cycle) was followed by an infusion of hyperkalemic solution (K+ concentration of hyperkalemic solution was 5.64 mmol/L and the osmolarity of hyperkalemic solution was unchanged) for three cycles, then normal K+ cancentration was recovered for two cycles;②The control period was followed by an infusion of L type Ca2+ channel blocker nifedipine (1.0 μmol/L) for three cycles;③L type Ca2+ channel inhibitor nifedipine (1.0 μmol/L) was infused for 36 rain prior (three cycles) to infusion of hyperkalemic solution. Atrial stroke volume was determined and the ANP secretion was measured by radioimmtmoaasay. Results (1)Hyperkalemic solution increased atrial ANP secretion (P<0.01) and reduced the atrial stroke volume,hut the difference was not statistically significant as compared with that of the control cycle(P>0.05). The recovery trend was to the normal level of ANP secretion and atrial stroke volume was to become normal gradually when solution level recovered to normal ,which was not significantly different from that of the control cycle (P>0.05) ;②Nifedipine (1.0 μmol/L) also increased the atrial ANP secretion (P<0.01 or P <0.05) while decreasing atrial stroke volume (P<0.01 or P < 0.05 ) ; ③Nifodipine (1.0μmol/L) completely blocked the effect of hyperkalemic solution so to increase the ANP secretion (P <0.01 ). Conclusion Hyperkalemic solution significantly increases atrial ANP secretion via extracellular high K+ competitive inhibition of extracellular Ca2+ inflow in beating rabbit atria.

Adult ; Female ; Humans ; Liver ; pathology ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease ; pathology ; Obesity ; pathology ; Young Adult

A HPLC method was established to determine the contents of the five anthraquinones and rhaponticin in the different varieties of Rhei Radix et Rhizoma. The difference existed in different varieties. The results showed that rhein and rhaponticin were marker substances which could be used to distinguish palm leaf groups rhubarb and wave leaf groups rhubarb. Authentic rhubarb didn't contain rhaponticin. Falsify rhubarb contains trace amounts of rhein. Rheum tanguticum contains abundant rhein. The ratio value of the content of rhein to chrysophanol could be used to distinguish R. tanguticum from the other two authentic varieties (R. palmatum and R. officinale). The content of rhaponticin varied largely in different varieties of wave leaf groups rhubarb.
Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; analysis ; Quality Control ; Rheum ; chemistry ; classification ; Rhizome ; chemistry ; classification

There have been very few studies on the effect of Gualou Xiebai Banxia decoction combined with Xuefu Zhuyu decoction in inhibiting apoptosis in myocardial ischemial injury caused by coronary heart disease. In this experiment, Gualou Xiebai Banxia decoction combined with-Xuefu Zhuyu decoction were used to intervene the miniature swine phlegm and blood stasis type coronary heart disease model, in order to observe the effect of the combined prescription on the myocardial apoptosis and the expressions of Bcl-2, Bax, Caspase-3, Caspase-9 in the model. Totally 15 Chinese experimental miniature swine were adopted and randomly divided into the control group, the model group and the phlegm and stasis-treating group. The model group and the stasis-treating group were fed with high fat diets for two weeks, intervened with the coronary artery injury and then given drugs and high fat diets for eight weeks. The control group was fed with ordinary diets for 10 weeks, without the coronary artery injury. After the experiment, myocardia at the juncture of infracted areas were collected and made into formalin-fixed paraffin sections. The TDT-mediate dUTP nick end labeling (TUNEL) assay was used to detect the myocardial apoptosis. The immunohistochemistry (IHC) technique was applied to detect Bcl-2, Bax, Caspase-3, Caspase-9 levels in myocardial tissues. According to the findings, the apoptosis indexes (AI) for the control group, the model group and the phlegm and stasis-treating group were 0.92%, 27.68%, 17.28%, respectively. The AI of the phlegm and stasis-treating group was significantly lower than that of the model group (P < 0.01). Compared with the model group, the phlegm and stasis-treating group showed significantly higher Bcl-2 protein expression (P < 0.01) and lower Bax, Caspase-3 and Caspase-9 protein expressions (P < 0.01). In conclusion, Gualou Xiebai Banxia decoction combined with Xuefu Zhuyu decoction have a significant protective effect against the myocardial apoptosis in miniature swine phlegm and blood stasis type coronary heart disease model.
Animals ; Apoptosis ; drug effects ; Caspases ; metabolism ; Coronary Disease ; drug therapy ; Disease Models, Animal ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Male ; Medicine, Chinese Traditional ; Myocardium ; pathology ; Phytotherapy ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; Swine ; Swine, Miniature ; bcl-2-Associated X Protein ; analysis

Objective To study the changes and management of systemic and pulmonary hemodynamics during anhepatic period in patients undergoing orthotopic liver transplantation without veno-venous bypass.Methods Sixty-eight patients with end-stage liver disease undergoing orthotopic liver transplantation were enrolled in this research. Monitoring and recoding CVP, MAP, CI, HR, MPAP, PAWP PVR, SVR at different time points: preincision, before anhepatic, 5, 30 min of anhepatic, 5, 30, 60 min of neohepatic,ending of operation, 12 h and 24 h after operation. All the patients were divided into three groups according CVP during anhepatic period: group A(CVP <4 mmHg) ,group B(4 mm Hg≤CVP≤6 mmHg) ,group C (CVP>6 mmHg). Besides, calculating the concentration of dopamine, norepinephrine ,epinephrine and the volume of urine during of operation. Results There were different changes during different operation periods. During anhepatic period, HR, PVR and SVR increased, while CVP, CI, MAP, PAP, PAWP decreased(P<0.05). At early neohepatic period, HR decreased and CVP,PAWP, MPAP,CI,PVR SVR increased ,At the beginning of neohepatic period, MAP dacreased or increased quickly, and became steadily after 5 min. Among the three groups, the changes of hemodynamics in group B was slightest,and the concentration of dopamine, norepinephrine and epinephrine was smallest (P< 0.05 ). Conclusions The systemic and pulmonary emodynamics fluctuated sharply during anhepatic and early neohepatic period. It is important and useful to manage CVP 4 -6 mmHg, MABP ≥ 60 mmHg by infusing liquid and vasoconstrictors,such as dopamine, norepinephrine or epinephrine during anhepatic period.

Based on the character of the molecular structure, the prodrugs of phosphates and phosphonates were divided into two categories. The first is the drug which contained the phosphate group, introducing protected groups to increase lipophilicity and improve bioavailability. The other one is the drug which had no phosphate group, introducing the phosphate group into molecules to enhance the solubility, regulate the distribution coefficient and enhance the drug-like property. This review focuses on the application of phosphates and phosphonates in drug research and development based on improvement of physico-chemical property, drug safety and the pharmacokinetics.