Objective To investigate the effect of different concentrations of dexmedetomidine on the apoptosis of hippocampal neurons in neonatal rat induced by propofol in vitro. Methods Hippocampal neurons of primary cultured neonatal SD rat were divided randomly into three groups. Group C (control group)was normal cultured without any treatment for 12 h; group P (Propofol group)was incubated with 12 μg/mL propofol for 12 h and group DP (Dexmedetomidine + propofol group)was incubated with 0.002 5 ~ 25 μg/mL dexmedetomidine for 30 min, and then further incubated with 12 μg/mL propofol for 12 h. Results Compared with that of group C, the apoptosis rate of hippocampal neurons increased in group P and DP (P < 0.05 or P < 0.01); Compared with that of group P, the apoptosis rate of neurons decreased with the increase of dexmedetomidine concentration in group DP (P<0.05 or P<0.01). The result of transmission electron microscope indicated that compared with group C , group P showed obvious neuronal damage; the nerve cells damage alleviated in group DP, which were negatively associated with the concentration. Conclusions With the concentration ranging from 0.002 5 to 25 μg/mL, dexmedetomidine set pre-incubation and breeding can reduce apoptosis of hippocampus neuron of neonatal rats induced by propofol and the effect is concentration dependent.

Objective To investigate the effects of different doses of remifentanil on learning and memory ability,the expression of hippocampal tissue phosphorylation of cAMP response element binding protein (p-CREB)in developing rats.Methods A total of 72 Sprague-Dawley rats (1 9-23 g) were randomly divided into 4 groups (n =18 each):Group C:normal saline control group;R1,R2, R3 group received continuous intraperitoneal remifentanil 1,5,10 μg·kg-1 ·min-1 for 2 hours re-spectively.Both total volume of remifentanil and saline were 2 ml.The SpO 2 and pulse rates were mo-nitored during the experiment.Step-down test was used to evaluate the learning and memory ability, while Western blot analysis was performed to measure the expression of hippocampal p-CREB protein in 4 h,24 h,1 week when the rats were awake.Results Compared with group C,group R1 and R2, pulse rates of group R3 decreased significantly (P <0.05 ),but the changes of SpO 2 in each group were not statistically significant.At 4 h point:compared with group C and group R1,the error times in step-down test were increased in both group R2 and R3,the latencies were shortened (P <0.05);Compared with group R2,the error times were increased in group R3,latency was shortened (P <0.05).At 24 h point,compared with group C and group R1,the error times were increased in group R2,R3,latencies were shortened (P < 0.05 );Compared with group R2,the error times were in-creased in group R3,latency was shortened (P <0.05 ).The error times and latency of each group had not statistical significance in one week.At 4 h point,the expression of p-CREB protein in hippo-campus of group R3 downregulated compared with group C and group R1,R2,respectively (P <0.05).At 24 h point,the expression of p-CREB protein in hippocampus of group R2,R3 decreased compared with group C and group R1 respectively(P <0.05);The expression of p-CREB protein in each group had no statistical significance in one week.Conclusion 5-10 μg · kg-1 · min-1 dose of remifentanil can result in a decline of learning and memory ability in the developing rats in short-term,and the mechanism may relate to the inhibition of p-CREB protein expression in hippocampus.

Objective To investigate the effect of hypothermia on the learning and memory a-bility of neonatal rats during anesthesia and its possible mechanism.Methods Forty SD rats aged 7 d were randomly divided into 4 groups (n=10):control group (group C),anesthesia group (group A),anesthesia and hypothermia group (group AH),hypothermia group (group H).Group C was in-jected intraperitoneally with 0.1 ml of saline and equipped with heating pad to keep the rectal temper-ature at 38-39℃.Group A was injected with propofol 0.1 ml at 25 mg/kg intraperitoneally with 1/2 of the initial dose,and anesthesia was maintained for 2 h.The same method to maintain the rectal temperature at 38-39℃;Group AH of anesthesia and time and Group A of the same,rats in the anes-thesia process is not insulation,control room temperature of 23℃,allowing the body temperature de-creased;Group H rats intraperitoneal injection of 0.1 ml saline,the same control room temperature of 23℃,so that the natural temperature drop.Anesthesia in the process of continuous oxygen,inter-mittent monitoring of body temperature.Immediately after awake,5 rats in each group were randomly selected to detect the content of p-ERK and p-CREB in hippocampus by Western blot.The spatial learning and memory ability and p-ERK and p-CREB contents in hippocampus were measured by water maze test.Results The rectal temperature in group AH and group H decreased to (25.38± 0.22)℃ and (25.54±0.20)℃ in 1 h respectively,and the body temperature decreased significantly compared with group C(38.36±0.24)℃ and group A(37.40±0.29)℃ (P<0.05).Compared with group C and group A,the expression of group AH and group H was decreased (P<0.05).At the end of the water maze test,the expression of protein in the four groups was not statistically signifi-cant.There was no significant difference between the four groups in the escape latency,the number of crossing the platform and the quadrant of the original platform quadrant.Conclusion The expression of p-ERK and p-CREB in neonatal rats hippocampus can be short-term inhibition in the period of hy-pothermia at 25℃,but no significant effect on the long-term learning and memory ability.

ObjectiveTo explore the mechanism of Renshen Baidusan in repairing intestinal mucosa in ulcerative colitis （UC） by regulating autophagy to scavenge peroxides. MethodThe mouse model of UC was induced by free drinking of 3.0% dextran sulphate sodium （DSS） solution. Sixty male C57BL/6J mice were randomized into normal， model， mesalazine （0.3 g·kg^-1）， and high-， medium-， and low-dose （12.35， 8.22， 4.11 g·kg^-1， respectively） Renshen Baidusan groups （n=10）. The mice were administrated with corresponding drugs by gavage for 7 consecutive days. The colon tissue was stained with hematoxylin-eosin （HE） to reveal the pathological changes， and Alcian blue-Periodic acid Scheff （PAS/AB） staining was employed to observe the goblet cell changes. The fluorescence expression of reactive oxygen species （ROS） in the colon tissue was detected by the immunofluorescence assay. The activity of superoxide dismutase （SOD） and the content of malondialdehyde （MDA） were measured by the biochemical methods. Western blot was employed to determine the expression levels of proliferating cell nuclear antigen （PCNA）， microtubule-associated protein 1 light chain 3 （LC3）， leucine-rich repeat-containing G protein-coupled receptor 5 （LGR5）， and p62. ResultDestroyed mucosal epithelial structure， intestinal gland destruction， loss of goblet cells， and massive infiltration of inflammatory cells appeared in the model group. Compared with the normal group， the model group showed increased tissue damage injury （TDI） score of the colon tissue， decreased SOD activity and LC3Ⅱ/Ⅰ， PCNA value， and elevated levels of p62， MDA， ROS， and LGR5 （P<0.05）. Compared with the model group， different doses of Renshen Baidusan decreased the TDI score， promoted the generation of new goblet cells， elevated the levels of PCNA， LGR5， SOD， and LC3Ⅱ/Ⅰ， and lowered the levels of p62， MDA， and ROS （P<0.05）. Moreover， the low dose group showed the best performance （P<0.05）. ConclusionRenshen Baidusan can promote intestinal epithelial repair by activating intestinal autophagy， alleviating oxidative stress， and promoting intestinal stem cell proliferation and differentiation.

ObjectiveTo explore the mechanisms of internal treatment （Renshen Baidusan）， external treatment （Yurui Enema）， and combination of the two methods in treating intestinal mucosal injury in the rat model of ulcerative colitis （UC） from the changes of phosphatidylinositol-3 kinase （PI3K）/protein kinase B （Akt）/nuclear factor-κB （NF-κB） pathway. MethodFifty SPF-grade SD rats were randomized into blank， model， Renshen Baidusan （15.6 g·kg^-1）， Yurui Enema （25 g·kg^-1）， and combined treatment （15.6 g·kg^-1 Renshen Baidusan + 25 g·kg^-1 Yurui Enema） groups （n=10）. The rat model of UC was established in other groups except the blank group by 2，4， 6-trinitrosulfonic acid （TNBS）/ethanol. The rats were administered with corresponding drugs once a day for 14 consecutive days since the 8th day after modeling. The histopathological changes of colon were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of tumor necrosis factor （TNF）-α， interferon （IFN）-γ， interleukin （IL）-4， and IL-10 in the colon tissue. The apoptosis of colon epithelial cells was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling （TUNEL）. The location and expression of B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， TNF-α， and IL-6 in the colon tissue were examined by immunohistochemistry. Real-time quantitative fluorescence polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of the proteins in the PI3K/Akt/NF-κB pathway in the colon tissue. ResultIn the model group， HE staining showed a large number of inflammatory cell infiltration in the mucosa and submucosa. Compared with the blank group， the model group showed elevated levels of TNF-α and IFN-γ and lowered levels of IL-4 and IL-10 in the colon tissue， increased apoptosis rate of colon epithelial cells， increased positive expression of Bax， TNF-α， and IL-6， and decreased positive expression of Bcl-2 （P<0.05）. Moreover， the model group showed up-regulated mRNA levels of PI3K， Akt， and NF-κB and protein levels of PI3K， p-PI3K， Akt， p-Akt， p65， p-p65， Bax， and cleaved Caspase-3， increased Bax/Bcl-2 and cleaved Caspase-3/Caspase-3 ratios， and down-regulated protein levels of NF-κB suppressor protein α（IκBα）， Bcl-2， and Caspase-3 in the colon tissue （P<0.05）. Compared with the model group， the internal treatment， the external treatment， and the combination （referred to as the three groups） alleviated the colonic mucosal injury， lowered the levels of TNF-α and IFN-γ and elevated the levels of IL-4 and IL-10 in the colon tissue， decreased the apoptosis rate of colon cells， inhibited the positive expression of Bax， TNF-α， and IL-6， and promoted the positive expression of Bcl-2 （P<0.05）. Furthermore， the combination group down-regulated the mRNA level of PI3K （P<0.05）. The three groups down-regulated the mRNA levels of Akt and NF-κB and the protein levels of p-PI3K， Akt， p-Akt， p65， p-p65， Bax， and cleaved Caspase-3 in the colon tissue， decreased the Bax/Bcl-2 and cleaved Caspase-3/Caspase-3 ratios， and up-regulated the protein levels of IκBα， Bcl-2， and Caspase-3 （P<0.05）. ConclusionRenshen Baidusan， Yurui Enema， and their combination may inhibit the activation of PI3K/Akt/NF-κB signaling pathway and regulate the expression of genes and proteins related to this pathway to achieve anti-inflammatory and anti-apoptotic effects， thus restoring the intestinal mucosal barrier function of UC rats.

ObjectiveTo study the mechanism of Renshen Baidusan in regulating adenylate-activated protein kinase （AMPK）/Unc-51-like kinase 1 （ULK1） autophagy pathway to inhibit mucosal barrier damage in the mouse model of ulcerative colitis （UC）. MethodSixty SD rats were randomized into normal， model， sulfasalazine enteric-coated tablets （0.312 5 g·kg^-1， western medicine）， and high-， medium-， and low-dose （31.2， 15.6， 7.8 g·kg^-1， respectively） Renshen Baidusan groups. The UC model was induced by 2，4，6-trinitrobenzenesulfonic acid （TNBS）/50% ethanol. The drugs were administrated by gavage for 2 weeks， and then the histopathological changes of the colon were examined. Real-time quantitative polymerase chain reaction was conducted to measure the mRNA level of AMP-activated protein kinase subunit alpha （AMPKα）. Western blot was employed to determine the protein levels of closure protein （Occludin）， compact linking protein-2 （Claudin-2）， autophagy marker p62， microtubule-associated protein 1 light chain 3B （LC3B）， phosphorylated AMPK （p-AMPK）， and phosphorylated ULK1 （p-ULK1）. ResultCompared with the normal group， the model group showed increased colon injury score （P<0.05）， down-regulated mRNA level of AMPKα （P<0.05） and protein levels of p-AMPK， p-ULK1， and Occludin， decreased LC3Ⅱ/Ⅰ ratio （P<0.05）， and up-regulated protein levels of p62 and Claudin-2 （P<0.05）. Compared with the model group， all the doses of Renshen Baidusan lowered the colon injury score， up-regulated the mRNA level of AMPKα and the protein levels of p-AMPK， p-ULK1， and Occluding， increased LC3Ⅱ/Ⅰ ratio， and down-regulated the protein levels of p62 and Claudin-2. Moreover， the medium-dose group showed a significant intervention effect （P<0.05）. ConclusionRenshen Baidusan can protect the intestinal mucosal barrier from damage， and the medium dose showed the best efficacy. It may activate the AMPK/ULK1 pathway to accelerate the transformation of LC3Ⅰ to LC3Ⅱ and promote the degradation of p62， so as to improve the function of Occludin and Claudin-2 and repair the mechanical damage of the intestinal barrier.

ObjectiveTo summarize the history and modern clinical application of Renshen Baidusan. MethodThe bibliometric method was used to retrieve the relevant publications of Renshen Baidusan from the ancient book database and China National Knowledge Infrastructure （CNKI）. The publications were screened according to the inclusion and exclusion criteria. The information of dynasty， book title， function， dosage and so on was extracted， on the basis of which the history， composition， dosage， decocting method， original medicinal plants， processing， and modern clinical application of this prescription were analyzed. ResultRenshen Baidusan was first recorded in the Formulary of the Bureau of Taiping People's Welfare Pharmacy， consisting of Bupleuri Radix， Glycyrrhizae Radix et Rhizoma， Platycodonis Radix， Ginseng Radix et Rhizoma， Chuanxiong Rhizoma， Poria， Aurantii Fructus， Peucedani Radix， Notopterygii Rhizoma et Radix， Angelicae Pubescentis Radix， Zingiberis Rhizoma Recens， and Menthae Haplocalycis Herba and with the effect of dispersing cold， removing dampness， reinforcing Qi， and relieving exterior. Later generations of physicians used this prescription on the basis of the record in Formulary of the Bureau of Taiping People's Welfare Pharmacy to treat cold （frequency of 112， 22.63%） and seasonal cold （frequency of 83， 16.77%）. Renshen Baidusan is widely used in modern clinical practice to treat respiratory diseases （frequency of 42， 17.65%）， skin diseases （frequency of 34， 14.29%）， and infectious diseases （frequency of 33， 13.87%）. This prescription is often modified to treat the syndrome of internal deficiency and external contraction， or external contraction of wind， cold and damp pathogens without deficiency of healthy Qi， which fully embodies the concept of treating different diseases with the same method in traditional Chinese medicine. ConclusionThe textual research reveals the key information of the classical prescription Renshen Baidusan， providing a basis for the subsequent development and application of compound preparations.