Lithocholic acid activates mTOR signaling inducing endoplasmic reticulum stress in placenta during intrahepatic cholestasis of pregnancy.

AIMS: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disorder, which increases risks of adverse fetal outcomes. However, the pathophysiology is not fully understood. Here, we explored the roles of mTOR signaling and ER stress in placenta during ICP. MATERIALS AND METHODS: Placental tissues were collected from normal and ICP pregnancies. mTOR signaling and endoplasmic reticulum stress were detected by immunohistochemistry in the placenta. The human placenta trophoblast cell line HTR-8/SVneo was used in vitro experiment. KEY FINDINGS: ICP placenta displayed histological abnormalities with fewer trophoblasts. Moreover, the expression of Bip and the phosphorylation of pS6(S235/236) or pAkt(S473) were higher comparing with normal placenta. In in vitro studies, the bile acids specifically to lithocholic acid rather than taurocholic acid or ursodeoxycholic acid, drastically increased the phosphorylation of pS6K1(T389), pS6(S235/236), or pAkt(S473), whereas the mTOR inhibitor can prohibit the upregulation. Similarly, the expressions of IRE1α and BiP increased sharply under lithocholic acid (20 µM) administration, while the same inhibitor can also decrease the expression. Additionally, transmission electron microscopy showed enlarged endoplasmic reticulum lumen under the lithocholic acid treatment. Furthermore, the cell viability reduced sharply under treatment with different dose of lithocholic acid. The mTOR inhibitor can reverse the decrease of cell viability to some extent. SIGNIFICANCE: Bile acid can activate mTOR signaling which resulted in endoplasmic reticulum stress, leading to trophocyte viability decrease. mTOR pathway activation may be associated with the pathophysiology of ICP.

Establishment of a rabbit model of heart failure by aortic regurgitation / 中国实验动物学报

Objective To establish a New Zealand rabbit model of heart failure by aortic regurgitation.Methods Adapting catheterization-induced aortic regurgitation to establish a volume overloat rabbit model of heart failure.The SBP, LVSP, LVDP, LV+dp/dt and LV ±dp/dt were observed before and after modeling.The successful criteria of heart failure:the LV ±dp/dtmax was decreased more than 40%and the LVDP increased more than 40%, or the LV ±dp/dtmax fell down to less than 40%and the DBP should be decrease more than 40%.Evaluating the model by observing the coat color, mental status, physical activity, calculating the feed consumption index, weight gain index, heart rate, respiration frequency and other indicators.The activity of serum SOD and MDA concentration were assayed to determine the antioxidant capacity of the model animals.Enzyme-linked immunosorbent assay kit was used to detect the serum cAMP and cGMP con-centration.Gene chip technology was used to analyze the difference of gene expression.Results After modeling, the he-modynamic index of SBP, DBP and LVSP were significantly decreased, LVDP was significantly decreased, LVDP was sig-nificantly increased and the LV+dp/dt and LV ±dp/dt were significantly decreased.Compared with the normal control group, the model animals showed coat withered, less movement, less eating, unresponsiveness, listlessness, and reduced grab resistance after modeling.The respiratory rate of the model group was significantly increased, and this trend was in-creased over time.The serum SOD activity was lower, MDA concentration was higher, cAMP concentration was lower, and cGMP concentration was higher in the model group.665 differentially expressed genes were detected.Compared with the human gene sequences, 16 characteristic genes were obtained.In these 16 genes, which were closely related to heart func-tion, were mainly related to ion channels, muscle contraction, and signal transduction function.Conclusions This repor-ted method to establish rabbit model of heart failure by using aortic regurgitation is reliable.The aortic regurgitation increa-ses cardiac preload, than leads to an increase of the left ventricular end-diastolic volume, and finally results in left ventric-ular hypertrophy and heart failure.The results of myocardial tissue gene chip test show that there are some changes in gene expression of the model rabbits.

Influence of Secretio Bufonis Injection on Mean Survival Time and Carcinostatic Activities in Mice Bearing Intraperitoneal H22 Tumor / 中国中医药信息杂志

Objective To investigate the mechanism of Secretio bufonis injection on the carcinostatic activities in mice bearing intraperitoneal H22 tumor. Methods Secretio bufonis injection (1.5 mL) was injected into the abdomind cavity of mice once 5 d for 3 times. Cyclophosphamide (0.5 mg/0.5 mL) was injected into other groups. NS (0.5 mL) was injected into control groups. Each group were 20 mice. TNF and survival time of mice were observed. Results Mean survival times of mice bearing intraperitoneal H22 tumor were (28.2?5.8)d for Secretio bufonis group,(27.9?9.7)d for Cyclophosphamide group,(20.7?4.2)d for control group. The content of TNF in mice bearing intraperitoneal H22 tumor were 2.53?0.14 for Secretio bufonis group,3.02?0.14 for Cyclophosphamide group,3.32?0.2 for control group. The survival times of mice bearing intraperitoneal H22 tumor were prolonged in the groups of Secretio bufonis (P

Experimental study on Modified Simiao Powder in treating polymyositis with damp-heat syndrome / 中华中医药杂志

Objective:To observe the mechanism and effect of Modified Simiao Powder on experimental polymyositis with damp-heat syndrome.Methods:The immunization combined with damp-heat syndrome modeling method was used to set up damp-heat model of polymyositis in guinea pigs.Methods of pathology,electron microscopy,electromyography,serum muscle enzymes were used to observe and compare the effects of Modified Simiao Powder and prednisone.Results:After treatment,the average time and improved degree of volatility of EMG in high dose herbal group were more superior to the prednisone group;the serum CPK,LDH,AST in all treatment groups decreased at different degree.The serum muscle enzymes in Chinese combined Western medicine group were significantly lower than other groups.In the changes of muscle,liver tissue pathology and ultra-structure,high-dose of Chinese herb showed more significant improvement than prednisone group,and the most significant improvement of interstitial pneumonia was observed in Chinese combined Western medicine group.Conclusion:Modified Simiao Powder has good effect on experimental polymyositis with damp-heat syndrome,it can inhibit cellular immune response and control the inflammatory cell infiltration,which may be involved in regulating the whole immune system.

Changes of Plasma Endogenous Peptides and Its Effect on Gestational Function in Endometriosis Rats / 广州中医药大学学报

【Objective】To observe the effect of plasma ?-endogenous peptides (?-EP) on gestational function in endometriosis(EMT) rats.【Methods】 Female SD rats at the third estrous cycle were used to establish EMT model.Then 20 EMT rats were equally randomized into the model group and naltrexone(an opioid receptor antagonist) group,and other 10 rats were in the pseudo-operation group.Naltrexone group was given naltrexone 2?mg?kg~-1?d~-1 by gastric gavage during proestrus and normal saline at other time,and the model group and pseudo-operation group were given normal saline for one month.Serum levels of ?-EP,luteinizing hormone(LH) and prolactin(PRL) were examined during proestrus,and serum progesterone(P) level and gestational function were observed after estrus.【Results】Serum levels of ?-EP and PRL increased and LH decreased during proestrus,and serum P level also decreased after estrus in the model group(P

Therapeutic Effect of Jade Maid Decoction for Experimental Periodontitis in Rabbits / 广州中医药大学学报

Objective To observe the therapeutic effect of Jade Maid Decoction(JMD),a Chinese herbal prescription for nourishing yin and clearing stomach-heat,on experimental periodontitis.Methods Twenty-four New Zealand rabbits were randomized into the model group,JMD group(oral use of JMD 23 g?kg-1?d-1),external application group(periodontal injection of minocycline hydrochloride ointment 50mg),and the combination group(oral use of JMD and periodontal injection of minocycline hydrochloride ointment).Experimental periodontitis was induced by ligation method.The treatment lasted 6 weeks.Gingival bleeding on probing(BOP) and probing pocket depth(PPD) were detected each week after medication,and pathological examination of the mandible was used to confirm the therapeutic effect after treatment.Results Gingival BOP was reduced to various degrees at different time in the three medication groups,and the effect was obvious in the combination group;PPD was also decreased to various degrees,and the difference of PPD between the three medication groups and the model group was significant after treatment for 4 weeks(P