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Aim To explore the diuretic effect, diuretic mechanism and pharmacokinetics of Phytolacca acinosa Roxb., and clarify its "quantity-time-effect" relationship.Methods Firstly, qualified rats were modeled by water load model, given different doses of Phytolacca acinosa Roxb.aqueous extract, then the diuretic effect was investigated.Secondly, Western blot was used to detect the protein expression of aquaporins AQP2, AQP4 and the angiotensin II receptors ATGR1, ATGR2, and renin in the RAAS system in kidney tissues.Thirdly, the established LC-MS/MS biological analysis method was used to detect the esculentoside A(EsA)content in the plasma, calculate the pharmacokinetic parameters and analyze the correlation between the blood concentration and the drug effect.Results The water load model was successfully established.Compared with the model group, hydrochlorothiazide had a significant diuretic effect(P<0.01).Low, medium and high dose groups of Phytolacca acinosa Roxb.all had obvious diuretic effects(P<0.01), EsA also had a significant diuretic effect(P<0.05).Phytolacca acinosa Roxb.aqueous extract and EsA significantly down-regulated the expression of AQP2, AQP4, ATGR1 and renin protein.The pharmacokinetic results showed that the Cmax and AUC0-t of EsA in the plasma of rats in the low, medium, and high dose groups of aqueous extract increased with the increase of the dose.Conclusions Phytolacca acinosa Roxb.had a diuretic effect, which is related to inhibiting the expression of aquaporins AQP2 and AQP4 and inhibiting the expression of angiotensin II type 1 receptor and renin, thereby inhibiting the reabsorption of renal tubules and collecting ducts.
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OBJECTIVE: To observe the effect of moxibustion pretreatment at different time on serum hormone levels in diminished ovarian reserve (DOR) rats, so as to explore its protective mechanisms. METHODS: Forty female SD rats were randomly divided into control, model, moxibustion-1 (moxibustion was given 4 weeks before modeling), moxibustion-2 (moxibustion was given 2 weeks before modeling and 2 weeks from the 1st day on after modeling ) and moxibustion-3 (moxibustion was given 4 weeks from the 1st day on after modeling) groups (n=8 rats in each group). The DOR model was established by gavage of Tripterygium Glycosides (75 mg/kg) once daily for 14 days. Grain-moxibustion was applied to "Shenshu" (BL23) and "Guanyuan" (CV4) for 7 cones, 5 times a week for 4 weeks. The body weight and the ovary weight were recorded for calculating the ovarian index. The levels of serum anti-mullerian hormone (AMH), follicle stimulating hormone (FSH), estradiol (E2), androgen (T) and dehydroepiandrosterone (DHEA) were detected by ELISA. RESULTS: After modeling, ovarian index and serum AMH levels were obviously decreased (P<0.05), and the levels of serum FSH, E2, T and DHEA were significantly increased in contrast with the control group (P<0.05). Following intervention and compared with the model group, the serum FSH and DHEA levels of each moxibustion group were significantly reduced (P<0.05), the AMH levels significantly increased and E2 and T contents significantly decreased in the moxibustion-2 and moxibustion-3 groups (P<0.05). The serum FSH, E2 and T contents in moxibustion-2 group were obviously lower than those of the moxibustion-1 and moxibustion-3 groups (P<0.05). CONCLUSION: Moxibustion pre-treatment can improve ovarian reserve function in DOR rats, while the effect is different with different intervention time, and the best intervention time is pre-occurrence and early stage of DOR.
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OBJECTIVE： To study the dose-time-effect relationship of Tibetan medicine Rannasangpei in cerebral ischemic- reperfusion injury model rats with intragastric administration. METHODS： The rats were randomly divided into sham operation group （normal saline， 10 mL/kg）， model control group （normal saline， 10 mL/kg）， positive control group （nimodipine， 30 mg/kg）， Rannasangpei different dose groups （0.52， 1.04， 2.08， 4.17， 8.33， 16.67， 33.34， 66.68， 133.36， 266.72 and 533.44 mg/kg）， with 18 rats in each group. Each group was given relevant medicine intragastrically once； 25 min after intragastric administration， cerebral ischemic-reperfusion injury model was established with suture-occluded method in those groups except for sham operation group. 24， 48， 72 h after cerebral ischemia， neuroethology of rats were graded in each group. The rate of cerebral infraction was detected to evaluate the optimal effective time， the optimal dose （Dmax） and maximal effect （the rate of minimum cerebral infraction， Emax） of Ratnasampil at different periods of cerebral ischemia. Dose-time-effect relationship of Rannasangpei dose with the rate of cerebral infraction was fitted with Thermo Kinetica 5.1 software. The area under curve （AUClast） and retention dose （MRTlast） of dose-effect curve were calculated， and detect the levels of SOD and MDA. RESULTS： Compared with sham operation group， the neurobehavior of model group was significantly abnormal （P＜0.05 or P＜0.01）， and the rate of cerebral infarction was significantly increased （P＜0.01）； the level of SOD was decreased significantly （P＜0.01， 48 h）， and the level MDA was increased significantly （P＜0.05， 48 h）. Compared with model control group， there was no significant change in neurobehavioral abnormalities in the nimodipine group （P＞0.05）， and the rate of cerebral infraction was decreased significantly （P＜0.01， 24， 48 h）. The level of SOD in rats were increased significantly （P＜0.01， 48 h）， while the level MDA decreased significantly （P＜0.05， 48 h）. Rannasangpei 2.08-33.34 mg/kg could significantly improved neurobehavioral abnormalities （P＜0.05， 24 h）； 24 h after cerebral ischemia， the rate of cerebral infraction was decreased significantly in Rannasangpei 4.17-133.36 mg/kg group （the lowest is 33.34 mg/kg group， P＜0.05 or P＜0.01）. The level of SOD in rats were increased significantly in 33.34-533.44 mg/kg groups （P＜0.05）. the level MDA was decreased significantly in 0.52-2.08， 8.33， 33.34， 266.72 and 533.44 mg/kg groups （P＜0.05）. Dmax was 33.34 mg/kg， Emax was 3.02％， AUClast was 5 141.76 mg/kg and MRTlast was 329.161 mg/kg. 48 h after cerebral ischemia， the rate of cerebral infraction was decreased significantly in Rannasangpei 2.08-133.36 mg/kg groups （the lowest is 66.68 mg/kg group， P＜0.05 or P＜0.01）， while the level of SOD was increased significantly in 1.04-533.44（except for 4.17）mg/kg groups （P＜0.05）. The level of MDA was decreased significantly in 16.67-66.68， 533.44 mg/kg groups （P＜0.05）， Dmax was 66.68 mg/kg， Emax was 2.13％， AUClast was 5 219.36 mg/kg and MRTlast was 340.521 mg/kg. 72 h after cerebral ischemia， the rate of cerebral infraction and the level of MDA had no significant decreased in Rannasangpei groups （P＞0.05）， and the levels of SOD had no significant increase （except for 0.52 mg/kg group， P＞0.05）. CONCLUSIONS： The optimal effective time of Rannasangpei for the treatment of cerebral ischemia-reperfusion injury in rats is 48 h， and the Dmax is 66.68 mg/kg. The improvement mechanism may be related to increase the level of SOD and decrease the level of MDA.
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<p><b>OBJECTIVE</b>To dynamically observe the effects of electroacupuncture (EA) on repair of gastric mucosal lesion in rats with gastric ulcer, and to explore the time-effect relationship and molecular mechanism of EA for gastric ulcer.</p><p><b>METHODS</b>A total of 72 SD rats were randomly assigned to a normal group, a model group, a acupoint group and a sham acupoint group, and each group were further divided into a 1-day subgroup, a 4-day subgroup and a 7-day subgroup, 6 rats in each subgroup. The rat model of gastric ulcer was established by using intragastric administration of ethyl alcohol. The rats in the acupoint group were treated with EA at"Zusanli"(ST 36) and"Liangmen"(ST 21); the rats in the sham acupoint group were treated with EA at points 5 mm next to"Zusanli"(ST 36) and"Liangmen"(ST 21); the EA was given 30 min per treatment, once a day. The rats in the normal group and model group were treated with immobilization for 30 min per day, and no EA was given. PR-PCR method was applied to test the expression of proliferating cell nuclear antigen (PCNA) and substance P (SP); Western blot method was applied to test the expression of neurotensin (NT).</p><p><b>RESULTS</b>After 1-day treatment, the ulcer index in the model group was higher than that in the normal group (<0.01), and the expression of PCNA, SP and NT was decreased (<0.01, <0.05); compared with the model group and sham acupoint group, the ulcer index was decreased in the acupoint group (both <0.05), and the expression of PCNA and SP was up-regulated (all <0.05) while that of NT was up-regulated (both <0.01). After 4-day treatment, the ulcer index in the model group was reduced but still higher than that in the normal group (<0.05), and the expression of PCNA, SP and NT was up-regulated and higher than that in the normal group (all <0.01); the ulcer index in the acupoint group was similar to that in the normal group (>0.05), and the expression of PCNA and SP was lower than that in the model group (<0.01, <0.05), and the expression of NT was not significantly different from that in the model group (>0.05). After 7-day treatment, the differences of indexes above were not significant among the four groups (all >0.05).</p><p><b>CONCLUSION</b>EA at acupoints of stomach meridian has two-way regulation on PCNA and SP and improve the expression of NT in different pathological state of gastric ulcer, which could further improve the repair of gastric ulcer.</p>
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In order to avoid international experts and scholars questioning the clinical effect of acupuncture, based on the traditional acupuncture theory and research reports, some questions are proposed from the research design, acupuncture effect and outcome explanation on the study ofpublished inin June 2017. And some thoughts and suggestions for the future development of the clinical acupuncture study are showed.
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Objective: To study the time-effect and dose-effect relationships of reducing uric acid of one complex extraction. Methods: Sixty male Kunming mice were randomly divided into blank group, model group, allopurinol group, and three groups of high, medium, and low complex extraction group. In the study of time-effect relationship, the mice were continuously treated with complex extraction for 2, 4, 7, 10, 13, 16, and 20 d, then the rats model was established by ip administration with oxonic acid potassium salt (20 mL/kg); In the study of dose-effect relationship, the mice were continuously treated with complex extraction for 7 d, then the rats model was established by ip administration with oxonic acid potassium salt (20 mL/kg). The mice urine, blood, and liver tissue were collected. Results: In the study of time-effect relationship, after 4 d of administration, the serum uric acid concentration was decreased obviously, and 7 d later, the low, medium, and high dose groups showed the significant activity of lowering uric acid, and the physiological and mental state of mice were very good in 20 d tests. Study on the relationship between dose and effect found that in low dose (100 mg/kg) showed good reduction of serum uric acid value activity (P < 0.05), and the high dose group (400 mg/kg) showed the most significant activity (P < 0.001). There was a certain dose-effect relationship. The high-dose group also showed significant inhibition of liver xanthine oxidase (XOD) activity (P < 0.05). Conclusion: The complex extraction has good reduction activity on uric acid in vivo, and shows certain dose-effect and time-effect relationships. The lowering effect on uric acid has relation with the inhibitory activity on xanthine oxidase.
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Objective To study the dose-effect relationship and time-effect relationship of T cell receptor (TCR) gene mutation induced by γ-rays in lymphocytes of human peripheral blood.Methods Samples of peripheral blood were collected from 10 healthy adults and lymphocytes were separated.Four samples from males used to fit time-effect curve were exposed to γ-rays at the doses of 0,0.5,1.0,1.5,2.0,2.5,3.0,3.5,4.0,and 5.0 Gy,respectively,and 6 samples from 3 males and 3 females used to fit dose-effect curves were exposed to γ-rays of the dose of 2 Gy.Flow cytometry was used to detect the mutation frequency of TCR gene (TCR MF).Radiation dose-effect curves and time-effect curves were fitted and optimal mathematical models were selected respectively.Results The optimal mathematical model for radiation dose-effect was quadratic equation model:TCR MF = 92.14 + 22.61D2 (R2adj = 0.65).The optimal mathematical model for radiation time-effect was quadratic polynomial equation model:TCR MF = 3.74 + 743.66T + 308.64T2 (R2adj = 0.79).Conclusions TCR MF is increased as the γ-rayirradiation dose increases within the range of 0-5 Gy,and TCR MF is increased with the lapse of time within the range of 4 days after γ-ray radiation.
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Objective To investigate the anti-tumor effects of photodynamie therapy(PDT)on human pancreatic cancer xenograft in nude mice and the time-effect relationship of PDT.Methods The animal model of human pancreatic cancer was developed by suturing small pieces of SW1990 tumors into the dorsum of nude mice.When the size of the tumors increased to 0.8～1.0 cm.36 mice were randomly divided into three groups:control group(no treatment),photosensitizer group(Photosan 2mg/kg,abdominal cavity injection),photodynamic group(Photosan 2 mg/kg injection+laser irradiation).Each group included 12 mice.The tumor sizes were measured twice per week and the weight8 and volumes of the tumors were measured,and the tumor inhibitory rate was calculated three weeks later.Results The tumor volume of photodynamic group was (0.22±0.12)mm3 at the 6th day,which was significantly smaller than(0.43 s0.18)mm3 of control group and(0.39±0.15)mm3 of photosensitizer group(P＜0.05).15 days later,the tumor volumes of PDT groups increased.21 days later.the weight of the tumors in photodynamie group was(0.69±0.23)g,which was significantly lower than(1.65 ±0.21)g of control group and(1.62±0.12)g of photosensitizer group(P＜0.05).The tumor inhibitory rate in photodynamic group was 58.18%,which was significantly higher than that of photoseasitizer group(1.8%,P＜0.05).Conclusions Photodynamie therapy had significant anti-tumor effect on human pancreatic cancer with quick-acting efficacy,but photodynamie therapy alone exeaed efficacy only in the shoa term.
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AIM: To investigate the dose and time-effect relationship of 7 antimicrobial agents in experimental treatment of vibrio vulnificus infection in mice. METHODS: Vibrio vulnificus ( 6.0?10 11 CFU?L -1) was introduced intraperitoneally into the right abdominal cavity. After 1 h, 7 antimicrobial agents were given intraperitoneally using 5 dose levels respectively, and (were given intraperitoneally) using human therapeutic dose after 0.5, 1, 2, 3 h of infection, respectively. 7 antimicrobial agents were imipenem lcilastatin, chloramphenicol, doxycycline hydrochloride, netilmicin sulfate, cefoperazone sodium, piperacillin sodium, and levofloxacin lactate. The numbers of survival mice and the supermicrostructure change of organs were observed. RESULTS: With high dose of the seven agents, blood culture showed negative, and organ supermicrostructure injure recovered. 7 antimicrobial agents produced satisfactory therapeutic effect against experimental vibrio vulnificus infection using human therapeutic dose after 0.5～1 h of infection. Chloramphenicol, netilmicin sulfate, cefoperazone sodium and levofloxacin lactate had the better therapeutic effect after 2 h of infection, and weak effect after 3 h. Imipenem showed a weak effect. CONCLUSION: The treatments with these 7 antimicrobial agents early can obtain satisfactory therapeutic effect against experimental vibrio vulnificus infection in mice.