P-glycoprotein (P-gp) belongs to the member of the super-family of ATP-binding cassette (ABC) transporters. It is the 170KD glycoprotein which is the product of the MDR1 gene, located in chromosome 7q21. It is an ATP-dependent exported and oriented transporter and involved in various physiological functions as well as the transport process of many types of drugs in the body. The physiological function of P-gp is to pump the toxic metabolites out of the cell in order to reduce the accumulation of toxic products so as to protect the cells from the poison. However, in pathological condition, the drug which used to treat the disease may be pumped out of the cells by the P-gp. Therefore,the P-gp is the main cause of the multidrug resistance in clinical disease such as tumor and some neurologic diseases. The cross-resistance phenomenon is leading to poor efficacy for these diseases treatment.Panax notoginseng as the characteristic Chinese herbal medicine in Yunnan province, it has many significant effects in the treatment and prevention of many diseases such as cerebrovascular diseases. It can improve the blood hemorrheology,prevent the produce of the peroxy radical, alleviate intracellular calcium overload,treat inflammation,as well as improve the immune system function. Meanwhile, some research recently reported that it also has a considerable prospect with its multi-target and multi-channel regulation in the reversal of the MDR1 and the P-gp genes expression. This paper reviews the progress of the down-regulated expression of P-gp and MDR1 genes through different pathways, and the mechanism of Panax notoginseng and its monomer compositions on down-regulated the expression of the P-gp and MDR1 genes.

AIM: To study the effects of Ginkgo biloba extract (GbE) on cerebral ischemia-reperfusion injury. METHODS: Cerebral ischemia-reperfusion injury was produced by 10 min or 20 min occlusion of bilateral carotid arteries followed by 5 d or 1 d reperfusion in gerbils. Ninety-five gerbils were divided into 4 groups: sham-operation, ischemia-reperfusion, GbE 50 mg*kg-1 and GbE 100 mg*kg-1 groups. Drugs were given intragastrically 2 d prior to ischemia and during reperfusion. The effects of GbE on the contents of calcium, sodium, water in cortex, and lipid peroxide(LPO) in brain hemispheres, as well as the density of neuron in hippocampal CA1 sector were observed. RESULTS: GbE could reduce the increase of calcium, sodium, water content in a manner of dose-depedance. The dosage of GbE 100 mg*kg-1 could decrease the content of LPO and the mortality, increase the density of neuron in hippocampal CA1 sector. CONCLUSION: GbE has protective effects on cerebral ischemia reperfusion injury.

Objective To observe learning and memory behavior changes of one time cerebral concussion called pure cerebral concussion(PCC)and three times cerebral concussion called multiple cerebral concussion (MCC)after injured 24 days in rats.Methods A metallic pendulum striker device was deployed to duplicate PCC and MCC model in SD rata which were the complete closed head injury model.The animals were divided into PCC and MCC groups at random.One control group was used,each group has eight animals(n=8).One 8-arms radial maze was used to assessed each animal's capabilities,that is,spatial reference memory,working memory,spirited activity and take in food.Results Compared with control group,there were some significance(P＜0.05)in both experiment groups post injury,that was,(1)The food intake decreased,PCC group from the 1st to the 11th day(from 0.00±0.00 to 2.62±1.76)after injury,MCC group from the 1st day to the 24th day(from 0.00±0.00 to 0.75±1.48)after injury.(2)Spirited activity depressed,PCC group on the 1st to the 7th,13rd day(from 4.87±1.24 to 10.0±2.39)after injury,MCC group on the 1st to 8th,22nd day(from 4.25±5.03 to 9.37±4.20)after injury.(3)The spatial reference memory was lower in early then gradually increased,PCC group on the 1 st to 7th day(from 0.50±0.75 to 3.O0±1.06)after injury,MCC group from the 1st to 19th day(from 1.88±2.10 to 2.50±2.44)after injury.(4)The working memory was delaying damaged,PCC group from the 1st to the 6th day and the 10th to the 23rd day(from 0.00±0.00 to 4.25±3.05)after injury,MCC group on the 1～4th,6th,9～13th,15th,16th,19th～22nd day(from 0.25±0.46 to 3.12±2.87)after injury.Conclusion The injured rata'capability of spatial reference memory,working memory,spirited activity and food intake were obviously damaged after CC,and the MCC group's capability of spatial reference memory,spirited activity and food intake was worse than PCC group.

ObjectiveTo observe the prepulse inhibition(PPI) ot the startle reflex of pure cerebral concussion (PCC) suffered from one concussion and multiple cerebral concussion (MCC) suffered from three concussions in rats,and to explore accumulate effect upon cognitive dysfunction of MCC.MethodsA metallic pendulum striker device for closed head injury was employed to duplicate PCC and MCC models in Stragu-Dawley rats.The MCC rats were hit three times on rats'head and it is interval 24 hours for every hit.According to the criteria of cerebral concussion,the investigated animals were divided into PCC group and MCC group at freedom.One control group was used.Each group included 10 animals.Each experience mental animal was tested from 3 days pre-injury to 28 days post-concussion.Startle reflex amplitude (for P values),pre-stimulation induced reflex amplitude on three standard stimulations,that was,67dB,69dB and 73dB (for PP67,PP69 and PP73 values) and prepulse inhibition of the startle reflex (PPI) were collected.ResultsThe P values and three PP values in the first three days of pre-replication experiment,there was no statistical significance in each group.However the P values and PP67,PP69 and PP73 values declined until to the 16th day after injury (P＜0.05),then recovered in PCC group.The P value and PP67,PP69 and PP73 values changes of MCC group declined and not recovered until to test end (P＜0.05 ) and they were more lower than PCC.The three PPI values were a little bit increase in both groups,there were statistics significance at some test points (P＜0.05) compared with control.ConclusionThe startle reflex amplitude and pre-stimulation induced reflex amplitude weaken after cerebral concussion and there is damaging accumulate effect to injury times,the PPI is enlanced by cerebral concussion.

Objective To observe the changes of the expression of P-glycoprotein(P-gp) after 90 min focal cerebral ischemia reperfusion in rats.Methods The model of.focal cerebral ischemia induced by blocking middle cerebral artery was made by using an intraluminal filament technique.A total of 26 adult SD male rats was used for experiment.One of them was applied for the 2,3,5-triphenyl tetrazolium chloride(TTC) staining to detect whether the focal cerebral ischemia model was successfully made,and the remaining rats were randomly divided into control group(n =5),sham operation group(n =5),and cerebral ischemia reperfusion for 1,3,7 d group(n=5).The immunohistochemistry single staining was used to observe the changes of P-gp in the normal and repefued ischemial brain tissue.The immunofluorescence double staining was used to observe the expression of P-gp in the normal and repefued ischemial brain tissue with Mdr-1 antibody,Neun antibody(marker of the neuron),GFAP antibody(marker of the astrocytes),and CD31 antibody(marker of capillary endothelium).Meanwhile the changes of P-gp in ischemic cerebral cortex and striatum capillary were analyzed by using real-time quantitative PCR technique.Results In control group,P-gp was only located in cerebral microvascular endothelial cells,while in cerebral ischemia reperfusion group,it also could be detected in some neurons and astrocytes.After cerebral ischemia reperfusion,the mRNA expression of P-gp in cerebral cortex was decreased on day 1,significantly increased on day 3,and then decreased on day 7.There was significantly statistical difference of the mRNA expression of P-gp cortex in cerebral ischemia reperfusion for 1,3,7 d group compared with control group and sham group(P＜0.05).After cerebral ischemia reperfusion,the mRNA expression of P-gp in cerebral striatum was increased on day 1,day 3and day 7,especially on day 1 and day 7,and the difference in cerebral ischemia reperfusion group was statistically significant compared with the other two groups (P＜0.05).Conclusion P-gp can only be expressed in cerebral microvascular endothelial cells in normal rats,while it can also be expressed in neurons and astrocytes in rats after the brain's subjection to ischemia reperfusion,and it showed different tendencies between cortex and striatum,which may be regarded as one of the self-protection mechanisms in brain tissue.

Objective To detect the long term effect of pure and multiple concussions on spatial cognitive of rats.Methods One hundred and eighty 7-week-old Spragne-Dawley male rats with weight of 280 ± 30g were chosen and randomly divided into a control group and a concussion group.The cerebral concussion was induced in the rats using a metallic pendulum striker concussive device.After the first strike,the brain injury group was randomly divided into a pure cerebral concussion(PCC)group and a multiple cerebral concussion(MCC) group.After the second strike,the MCC group was randomly divided into two-fold cerebral concussion(2MCC) group and three-fold cerebral concussion(3MCC) group.The striking interval was 24h.One,3 and 6 months after trauma,their cognitive function was tested using Morris water maze.Results One month later after injury,there was no significant difference in the escape latency between the control group and PCC group.Significant differences in the measurement were observed between the control/PCC group and 2MCC group on the 7th day after the injury,also between the control/PCC and 3MCC groups on the 6th and 7th day.And there were significant differences between the 2MCC and 3MCC groups on the 6th and 7th days.The non-platform test did not observe any significant differences among the four groups.Three months after injury,there was still no significant difference between the control group and PCC group,PCC and 2MCC groups,as well as 2MCC and 3MCC groups in the escape latency.However,there was significant difference between the control group and 2MCC group on the 5th,6th and 7th days,between the control group and 3MCC group on the 4th,5th,6th and 7th days,as well as between PCC group and 3MCC group on the 6th and 7th days.In the non-platform test,there was no significant difference between the control group and PCC group,between PCC group and 2MCC group,as well as between 2MCC group and 3MCC group.However,2MCC and 3MCC groups spent significantly less time in the former platform quadrant,when compared with the control group and 3MCC group spent significantly less time than PCC group.Six months after injury,significant differences in the escape latency were observed between the control group and PCC group on the 6th and 7th days,and 2MCC group on the 5th,6th and 7th days,also and 3MCC groups on the 2nd,3rd,4th,5th,6th and 7th days,still between PCC group and 2MCC group on the 6th and 7th days,as well as between PCC group and 3MCC group on the 4th,5th,6th and 7th days.Moreover,there was significant difference between 2MCC and 3MCC groups only on the 7th day.In the non-platform test,PCC group,2MCC group and 3MCC group spent significantly less time in the former platform quadrant compared with the control group.Moreover,in this test significant differences were found between PCC group and 2MCC/3MCC group,but not between 2MCC group and 3MCC group.Conclusion With the increase of cerebral concussion times,earlier and more serious damage of spatial cognition will appear,with a significant cumulative effect in rats.Such rat model can be used to study the pathological changes of cognitive impairment in chronic traumatic encephalopathy.