ABSTRACT
Objective:To study the effect of insulin intraperitoneal administration combined with dietary intervention on glycemic regulation in in KKAy mice with spontaneous type 2 diabetes.Methods:An animal model of type 2 diabetes was established, and healthy C57BL/6J mice were selected as the normal control group and healthy KKAy mice as the non-disease group. The successfully modeled KKAy mice were randomly divided into the subcutaneous group, the intraperitoneal group, and the untreated group. The non-disease group was given a maintenance diet, and all other groups were fed a high-fat, high-sugar diet. The daily feeding time was from 08:00 to 20:00, with one feeding at a 4-hour interval, for a total of four times. The subcutaneous and intraperitoneal groups were given subcutaneous and intraperitoneal insulin injections before feeding, and recombinant glargine insulin injection (subcutaneous group: 0.125 IU/g; intraperitoneal group: 0.250 IU/g) was injected before the first feeding, and biosynthetic human insulin injection (subcutaneous group: 0.075 IU/g; intraperitoneal group: 0.125 IU/g) was injected after a 0.5 h interval; the rest 3 times before feeding, the biosynthetic human insulin injection (subcutaneous group: 0.075 IU/g; intraperitoneal group: 0.125 IU/g) was injected for 4 weeks. The dietary intake, body mass, fasting blood glucose, and 1 and 2 h postprandial blood glucose of mice in each group were tested regularly, and an oral glucose tolerance test was performed.Results:The total dietary intake of mice in the intraperitoneal group was lower than that in the subcutaneous group. Compared with the initial body mass, the body mass of the mice in the subcutaneous and intraperitoneal groups decreased by 5.05 and 3.59 g at week 4, respectively. The changes of fasting blood glucose in the subcutaneous and intraperitoneal groups ranged from 5.4 to 9.4 and 5.4 to 6.4 mmol/L, respectively, and the changes of 1 h postprandial blood glucose ranged from 4.6 to 12.3 and 5.7 to 8.9 mmol/L, respectively, and the changes of 2 h postprandial blood glucose ranged from 2.5 to 9.8 and 3.8 to 7.1 mmol/L, respectively. For the glucose tolerance index, the intraperitoneal group showed improvement at all time points, and the subcutaneous group showed a decrease at all time points except for 0 and 60 min.Conclusions:In combination with dietary intervention, insulin intraperitoneal injection was more effective in controlling blood glucose in KKAy mice with spontaneous type 2 diabetes compared with subcutaneous insulin injection, and had a significant improvement in glucose tolerance.
ABSTRACT
AIM: To optimize the technique of intravenous injection of Evans blue and retinal preparations in mice, improving the accuracy and repeatability of staining experiment of retinal preparations.METHODS: C57BL/6 male mice were intravenous injected with 10g/L(1%)Evans Blue 0.3mL and circulated in vivo for 10 or 20min, and the eyes were removed after sacrificed and fixed in 4% paraformaldehyde for 20, 40 or 60min. When failure of intravenous injection, the experiment was remediated by intraperitoneal injection of 1% Evans Blue 0.3mL, circulated in vivo for 3h and fixed for 60min to observe morphology, distribution and leakage of the retinal vessels. Besides, we compared the morphology, distribution and leakage of the retinal vessels after intravenous injection with those after intraperitoneal injection to determine the optimal conditions for in vivo circulation time and retinal preparations.RESULTS: After intravenous injection, compared to the retinal vascular condition under 20min in vivo circulation time of Evans blue and 20 or 40min of fixation, with 10min of in vivo Evans blue circulation and 60min of fixation, the morphology of retinal vascular was more intact with less retinal vascular leakage, and the vascular branches are clear. When intravenous injection failed, remediated results from intraperitoneal injection showed that the morphology and distribution of retinal vessels were intact. There was no significant difference in morphology, distribution and leakage of the retinal vessels after 3h of intraperitoneal Evans blue circulation compared to 10min intravenous Evans blue circulation.CONCLUSION: This experiment optimizes the protocol, improves the accuracy and reproducibility of retinal preparations, and provides a reference for the study of related retinal vascular diseases.
ABSTRACT
Objective:To observe the distribution of 177Lu-FA-DOTA-PEG-PLGA nanoparticles in vivo, and evaluate the therapeutic effect of nanoparticles intraperitoneal injection on ovarian cancer peritoneal metastases and ascites. Methods:Nanoparticles were prepared and injected into human ovarian cancer xenograft nude mice model by tail vein. Micro-SPECT/CT imaging was performed at different times (4, 24, 72 h and 7 d) after injection to observe the distribution of nanoparticles in vivo. Nude mouse models of intraperitoneal metastases of human ovarian cancer were randomly divided into negative control group (normal saline), chemotherapy group (cisplatin 3 mg/kg, twice a week) and nanoparticle group (18.5 MBq), with 4 mice in each group. After 7 days, intraperitoneal tumor growth was evaluated by in vivo fluorescence imaging. The relative tumor inhibition rate was counted. Tumor cell apoptosis rate was detected by TUNEL method, and the proliferation activity tumor Ki67 was detected by immunohistochemical method. The ascites volume of each group was compared after treatment. Results:Micro-SPECT/CT imaging showed the radioactive uptake of the transplanted tumor, and the 24 h tumor muscle uptake ratio (T/M) was the highest, about 2.81±0.49. Intravital fluorescence imaging showed that, after intraperitoneal administration, the fluorescence intensity of abdominal tumor in particle group, chemotherapy group and control group was (1.45±0.19)×10 10, (2.21±0.36)×10 10 and (2.63±0.79)×10 10( F=6.09, P=0.029), respectively. The relative tumor growth inhibition (TGI) of the particle group and the chemotherapy group were 35.6% and 18.6%, respectively. The tumor cell apoptosis rates in particle group and chemotherapy group were higher than those in control group ( F=9.96, P=0.009). Ki67 indexes in particle group and chemotherapy group were lower than those in control group ( F=9.93, P=0.013). The ascites volume in particle group and chemotherapy group were both smaller than those in control group ( F=13.43, P=0.006). Conclusions:177Lu-FA-DOTA-PEG-PLGA nanoparticles can be used for the targeted imaging of ovarian cancer. After intraperitoneal injection, nanoparticles show local retention, degradation and absorption and thus inhibit the growth of peritoneal metastases and ascites of ovarian cancer, which provides a new idea for the diagnosis and treatment of advanced ovarian cancer with peritoneal metastasis.
ABSTRACT
OBJECTIVE：To compare the protective effect of atomization inhalation and intraperitoneal injection of edaravone on acute lung injury in smoke inhalation lung injury model rats. METHODS ：Thirty male SD rats were divided into normal control group（group A ），injury group （group B ），intraperitoneal injection group （group C ），low-dose aerosol inhalation group （group D），high-dose aerosol inhalation group （group E ）according to random numble table ，with 6 rats in each group. Group B-E were placed in smoke generator containing pine sawdust to induce smoke inhalation lung injury model. In group A ，the operation was the same as above except that the pine sawdust was not placed. Thirty minutes after modeling ，group C were injected intraperitoneally with edaravone 18 mg/kg（every 70 min，4 times in total ）. Group D and E inhaled edaravone 9，1.8 mg/kg（every 60 min，lasting for 10 min each time ，4 times in total ）. The rats were treated by no means in group A and group B. Six hours after last medication，arterial blood gas analysis was performed ，and the lung wet to dry ratio （W/D）and water content of lung tissue were calculated. The levels of TNF-α，IL-6 and IL- 10 in serum were detected by double antibody ELISA. The contents of MDA ，MPO， SOD and Caspase- 3 in lung tissue were determined by ELISA and other methods. HE staining was used to observe the pathological changes of lung tissue. The apoptotic rate of cells in lung tissue were determined by TUNEL assay. RESULTS ：No abnormality was found in lung tissue of group A ；in group B ，hemorrhage and edema were found in lung tissue ，alveolar structure was difficult to identify，and inflammatory cells and red blood cell infiltration were seen. Above symptoms of rats in group C-E were improved to different extent. Compared with group A ，PaO2/FiO2 and SOD content of lung tissue were decreased significantly in other groups （P＜0.05）；water content of lung tissue ，W/D，serum contents of TNF-α，IL-6 and IL- 10，the contents of MDA ，MPO and Caspase-3 in lung tissue ，apoptotic rate were increased significantly （P＜0.05）. Compared with group B ，PaO2/FiO2 and serum contents of IL- 10 were increased significantly in administration groups （P＜0.05）；water content of lung tissue ，W/D，serum contents of TNF-α and IL-6，the contents of MDA ，MPO and Caspase- 3 in lung tissue ，apoptotic rate were significantly decreased，in dose-dependent manner （P＜0.05）. CONCLUSIONS ：Edaravone has a certain protective effect on smoke inhalation lung injury model rat. It can reduce the production and release of inflammatory mediators and/or cytokines ，reduce the peroxide damage and inhibit cell apoptosis in a dose-dependent manner. The effect of atomization inhalation is more obvious than that of intraperitoneal injection.
ABSTRACT
BACKGROUND: Axons do not regenerate after central nervous system injury in mammals. It is mainly caused by the inhibitory microenvironment at the site of damage and the weakened self-regeneration ability. Studies have found that peripheral nervous system has certain regeneration ability after injury, so we explore the methods of central nervous system repair by studying the genes promoting peripheral nervous system regeneration. As one of the important protein kinase families of neurons, CaMKII up-regulation can improve the ability of neuron regeneration. Similarly, acute depletion of the Smad1 protein in adult mice also prevented axon regeneration in vivo. These genes can directly or indirectly regulate neuronal axon regeneration, but exactly how they regulate neuronal regeneration is still unclear. OBJECTIVE: To study the effects of CaMKII-Smad1 signaling pathway on axon regeneration of dorsal root ganglion neurons by intraperitoneal injection of CaMKII inhibitor and activator, and explored the mechanism of CaMKII and Smad1 in regulating axon regeneration of dorsal root ganglion neurons. METHODS: Totally 40 ICR mice were randomly divided into four groups: KN93 control group, KN93 experimental group, CdCl2 control group and CdCl2 experimental group. Dorsal root ganglion tissue was taken for in vitro culture after 7 days of continuous administration of CaMKII inhibitor KN93 and activator CdCl2. The length of axonal regeneration of dorsal root ganglion neurons was statistically analyzed after 3 days. Protein expression of p-Smad1 in dorsal root ganglion neurons was detected using western blot assay. RESULTS AND CONCLUSION: (1) Compared with the KN93 control group, axonal regeneration of dorsal root ganglion neurons was inhibited, and the p-Smad1 protein expression was decreased in the KN93 experimental group, showing significant differences. (2) Compared with the CdCl2 control group, axonal regeneration of dorsal root ganglion neurons was promoted, and p-Smad1 protein expression was increased in the CdCl2 experimental group, showing significant differences. (3) The results showed that the CaMKII-Smad1 signaling pathway had a regulatory effect on axonal regeneration of dorsal root ganglion neurons.
ABSTRACT
Objective: To establish a UPLC-MS/MS analysis method for determination of baicalin, geniposide, chlorogenic acid, cholic acid and hyodeoxycholic acid in Qingkailing (lyophilized) for injection in rat plasma, and to investigate the pharmacokinetic behavior of this preparation in normal and cerebral ischemic rats. Method: Rats were randomly divided into normal group and cerebral ischemia model group. The rat model of cerebral ischemia was established by suture embolization. The rats were given by intraperitoneal injection, and normal saline was used as the solvent. Blood samples were taken at the corresponding time points. After treatment, UPLC-MS/MS was used to determine the blood concentration of five components. The main detection conditions were mobile phase of 0.1%formic acid aqueous solution-acetonitrile for gradient elution (0-0.25 min, 90%A; 0.25-1 min, 90%-75%A; 1-2 min, 75%-50%A; 2-2.6 min, 50%-45%A; 2.6-2.65 min, 45%-90%A; 2.65-4.0 min, 90%A), the flow rate of 0.4 mL·min-1, the column temperature at 40℃, electrospray ionization under negative ion mode. The pharmacokinetic parameters were fitted and the bioavailability was calculated, the differences of treatment process of five components from Qingkailing (lyophilized) for injection in normal and cerebral ischemic rats were analyzed. Result: Compared with the normal group, the area under the curve (AUC0-t) of geniposide in rats from cerebral ischemia model group decreased significantly after intraperitoneal injection of Qingkailing (lyophilized) for injection (PTmax) of chlorogenic acid in rats from cerebral ischemia model group was significantly earlier than that in the normal group (PConclusion: Qingkailing (lyophilized) for injection has a certain difference in the treatment process between normal and cerebral ischemic rats, which has certain guiding significance for the clinical treatment of cerebral ischemic diseases with this preparation.
ABSTRACT
Objective To compare the effects of isoflurane and pentobarbital on the establishment of subarachnoid block model in rats.Methods 60 SD rats aged 4 months were randomly divided into Group A (n =30) and Group B (n=30).Rats in Group A received intraperitoncal injection of 10 g/L pentobarbital sodium solution 30 mg/kg and 1/4 of the initial dosage was added according to the operation effect.The induction and maintenance of anesthesia were achieved by isoflurane inhalation in Group B during operation.We recorded the time of anesthesia induction,quality of anesthesia,time of anesthesia,time of operation,and recovery time.The heart rate,respiration frequency,temperature,and saturation of blood oxygen were recorded during operation.We compared death from anesthesia and success of modeling in the two groups.Results There was no significant difference between the groups with regard to age,weight,body temperature or saturation of blood oxygen (P＞ 0.05).Compared to Group B,heart rate decreased 1-60 minutes after anesthesia and respiration frequency decreased 5 minutes after anesthesia in Group A (P＜0.05).The time of anesthesia induction,time of anesthesia,time of operation,and recovery time were shorter in Group B (P＜0.05).The quality of anesthesia was better in Group B (P＜0.05).The success rate of modeling was higher but mortality rate of anesthesia was lower in Group B than in Group A (P＜0.05).Conclusion Compared with intraperitoneal injection of pentobarbital sodium,isoflurane inhalation can provide a better anesthetic effect during the operation to establish a rat model of subarachnoid block.
ABSTRACT
OBJECTIVE:To observe the effects of single administration of carboplatin by different ways on drug accumulation concentration and treatment of tumor tissue before surgery. METHODS:60 patients with resectable advanced gastric cancer were randomly divided into intraperitoneal administration group(30 cases)and intravenous administration group(30 cases). All patients received 50 mg/m2 Carboplatin injection,intravenous administration,it stopped 4 weeks after continuous 5 d,repeated 3 times, when the last chemotherapy,intraperitoneal administration group was given 30 mg/m2 Carboplatin injection,adding into 750 ml 0.9% Sodium chloride injection,and placed in 37 ℃ water bath for preheating,taking paracentesis for disposable rapid injection. Intravenous administration group was 30 mg/m2 Carboplatin injection,adding into 750 ml 0.9%Sodium chloride injection,by intra-venous infusion within 30 min. Both groups were administered once for at least 1 week,then surgery was taken after 5 d. The car-boplatin accumulation concentration in 2 groups was determined after 160-180 min and 250-260 min,respectively,and the efficacy in the 5th day and incidence of adverse reactions during treatment were recorded. RESULTS:The total effective rate after 5 d,peri-toneal fluid,portal vein and peripheral blood after 160-180 min,and carboplatin accumulation concentration in cancer tissues,adja-cent normal tissues,peritoneum,omentum and negative lymph node after 250-260 min in intraperitoneal administration group were significantly higher than intravenous administration group,the incidence of adverse reactions was significantly lower than intrave-nous administration group,the differences were statistically significant(P<0.05). CONCLUSIONS:Compared with intravenous in-fusion,intraperitoneal injection of carboplatin before surgery can improve the local accumulation concentration and chemotherapeu-tic effect and reduce incidence of adverse reactions.
ABSTRACT
Aim Carvacrol ( CAR ) , possesses a wide variety of pharmacological properties including antioxi-dant and anti-inflammatory potential. The present stud-y is designed to investigate the effect of CAR on glu-cose and lipid metabolism in type 1 diabetic mice. Methods Diabetes was induced by intraperitoneal( i. p) injection of streptozotocin into male mice at the dose of 45 mg·kg-1 body weight( BW) . Mice were divided into three different groups containing eight to twelve in each. Age matched male C57 mice were used as nor-mal controls. Group I diabetes, Group Ⅱ and Ⅱ in-jected with CAR at 10 and 20 mg · kg-1 BW respec-tively once daily. After CAR injection 2, 4 or 6 weeks, the rats were weighted and the plasma concen-trations of glucose, total cholesterol( TC) , triglycerides (TG), Glutamic oxalacetic transaminase(AST), Ala-nine transaminase( ALT) levels were enzymatically de-termined using commercial kits. Results STZ-induced C57 BL/6 J diabetic mice showed an elevation in serum glucose, TG, ALT, AST and LDH levels. Compared to diabetic mice, administration of CAR resulted in sig-nificant decreases(P <0. 05) in plasma glucose, TG and LDH levels in a dose dependent manner, but no effect on elevated TC, ALT and AST levels. Conclu-sion These major findings provide evidence that CAR has anti diabetic property and it has the potential for development into a drug to prevent hyperglycemia, re-duce blood lipids and protect the dammaged organs.
ABSTRACT
Objective To compare the advantages and disadvantages of two methods for rat overactive bladder(OAB)model construction in?duced by intraperitoneal injection and intravesical instillation cyclophosphamide. Methods A total of 30 female SD rats weighting 200?250 g were randomly categorized into three groups:intraperitoneal injection?induced OAB(Ip?OAB),intravesical instillation?induced group(Iv?OAB)and con?trol group. Ip?OAB rats was i.p. administrated cycbophosphe mide three times in dose of 75 mg/kg body weight,while Iv?OAB rats received intravesi?cal instillation three times in drug dose of 75 mg/kg body weight. Control group rats received no treatment. Maximum bladder capacity(MBC),maxi?mum voiding pressure(MVP),frequency of spontaneous contraction of each group were recorded. The incidence,the mortality and the pathology of the three groups were compared. Results MBC,MVP and frequency of spontaneous contraction between Ip?OAB group and Iv?OAB group had no statistically significant difference(P>0.05). Compared with the control group,MBC significantly increased(P<0.05),MVP significantly decreased (P<0.05),and frequency of spontaneous contraction significantly increased(P<0.05)in Ip?OAB and Iv?OAB rats. The modeling success rate and mortality were 100%and 80%in Ip?OAB group,and were 50%and 0%in Iv?OAB group,and pathological changes were found in the two groups. Conclusion The construction of experimental animal model of OAB in rat induced by intraperitoneal injection and intravesical instillation cyclo?phosphamide are both reliable methods. Ip?OAB rats exhibit high incidence and mortality rate,while Iv?OAB rats show low incidence and mortality rate.
ABSTRACT
BACKGROUND: Thalidomide has been recognized as having an anti-allodynic effect against neuropathic pain induced by spinal nerve ligation. Its clinical beneficial effects are mainly derived from its immune-modulating property, which is known to influence the analgesic action of morphine. The possible characteristics of systemic interactions between thalidomide and morphine in the context of spinal nerve ligation-induced neuropathic pain were examined in rats. METHODS: Neuropathic pain was induced by ligation of the L5/6 spinal nerves in male Sprague-Dawley rats and mechanical allodynia was assessed using von Frey filaments. The ED50 was calculated for thalidomide and for morphine, and the mixture of both drugs was intraperitoneally administered at different doses of ED50 of each drug (1/8, 1/4, 1/2, 1/1 of ED50) to obtain the experimental ED50 value for the combination of thalidomide and morphine. Isobolographic analysis was used to evaluate the characteristics of drug interactions between morphine and thalidomide. RESULTS: The ED50 of thalidomide was three-fold higher than that of morphine. The experimental ED50 value of the mixture of thalidomide and morphine was significantly lower than the calculated theoretical ED50 value. Isobolographic analysis revealed a synergistic interaction for anti-allodynic effect after intraperitoneal delivery of the thalidomide-morphine mixture. CONCLUSIONS: These results suggest that thalidomide acts synergistically with morphine to produce an anti-allodynic effect in neuropathic pain induced by spinal nerve ligation in rats. Thus, the combination of thalidomide with morphine may be one of the useful strategies in the management of neuropathic pain.
Subject(s)
Animals , Male , Rats , Analgesics , Drug Interactions , Drug Synergism , Hyperalgesia , Injections, Intraperitoneal , Ligation , Morphine , Neuralgia , Rats, Sprague-Dawley , Spinal Nerves , ThalidomideABSTRACT
Objective To study the role of recombinant human epidermal growth factor (rhEGF) in the prognosis of multiple organ dysfunction syndrome (MODS) in mice. Methods One hundred and twenty clean male Kunming mice were randomly ( random number) divided into normal saline control group (n =15),MODS model control group (n =15) and MODS + rhEGF treatment group (n =90).The MODS models were made by using Caballero ME method with thioacetamide (TAA) 2000 mg/kg injected intraperitoneally to establish monophasic rapid onset pattern of MODS model in mice.MODS + rhEGF treatment group was further randomly divided into two subgroups,namely intraperitoneal injection group (n =45 ) and subcutaneous injection group (n =45 ).Each subgroup was divided again into three small subgroups (n =15) as per different doses of rhEGF used,namely 10 μg/kg,30 μg/kg and 50 μg/kg.Within 24 hours after modeling,the respiration,body weight,food eaten and general physical changes were observed.Mortality was calculated 24 hours after modeling.After the animals sacrificed,the tissues of viscus including liver,kidney,heart,brain,lung,spleen,pancreas,intestine and stomach were collected immediately.The histological changes of visceral tissues were studied by using hematoxylin -eosin staining under the light microscope.All the experimental data were presented in,and body weight changes were compared using t-test,and after different routes of administration with different doses of rhEGF used in MODS,the mice body weight changes were analysed by using the Dunnett method,and the mortalities of mice were compared by using Fisher exact test,and P ＜ 0.05 was considered statistically significant difference. Results There was no significant difference in mortality betweeu mice in rhEGF subcutaneous administration group and MODS model control group (P ＞ 0.05 ),but the total mortality of hrEGF MODS intraperitoneal administration group (6.7％ in dose of 50 μg/kg and 20％ in dose of 30 μg/kg) was significantly lower than that of MODS model control group (73.3％) ( P ＜ 0.05 ) and the mortality of mice treated with intraperitoneal 50μg/kg rhEGF (6.7％ ) was lower than that treated with 10μg/kg rhEGF (P=0.014).The mortality of mice in rhEGF MODS (50 μg/kg ) intraperitoneal administration group was significantly lower than that in subcutaneous administration group (40％) (P =0.031 ), The histopathological changes in rhEGF MODS treatment group were not as remarkable as seen in mice of control group.The histopathological changes were dose - dependent.The higher doses of rhEGF,the lesser hepatic congestion,liver cell apoptosis,hepatic cell cloudy swelling and cell vacuolization.Similarly,as RhEGF dosage increased,pulmonary interstitial congestion,inflammatory cells and apoptotic bodies reduced,and bronchial ciliated columnar epithelium less shed.Conclusions RhEGF plays a positive role in repairement of tissue damage in TAA - induced MODS murine model.The rhEGF given by intraperitoneal route of administration is more effective to reduce the 24 h mortality of MODS mice than that by subcutaneous route.
ABSTRACT
Secondary hyperparathyroidism is a major complication in ESRD patients undergoing dialysis. In hemodialysis patients with secondary hyperparathyroidism, intravenous administration of paricalcitol became widely utilized. In CAPD patients, however, the intravenous administration of paricalcitol which requires frequent visits to the clinic is not practical. The subject of this study was one CAPD patient with secondary hyperparathyroidism. He had already received oral calcitriol pulse therapy for 6 months and thereafter refused parathyroidectomy and intravenous paricalcitol which required frequent visits to the hospital. Furthermore, paricalcitol capsule is not yet introduced in Korea. Consequently, intraperitoneal paricalcitol therapy was tried whereby the patient was taught how to inject the paricalcitol (5 ug) directly into the dialysate for three times per week before bedtime. Blood samples for measurement of intact parathyroid hormone (iPTH), serum ionized calcium, serum phosphate, serum total alkaline phosphatase levels were obtained at baseline and after 1, 2, 3 and 4 months of treatment. After usage of intraperitoneal paricalcitol for 2 months, there was a significant decrease in iPTH level. In conclusion, intraperitoneal paricalcitol therapy might be effective for suppressing iPTH in CAPD patients with secondary hyperparathyroidism. A large-scale and long-term study must be conducted for safety and clinical effect.
Subject(s)
Humans , Administration, Intravenous , Alkaline Phosphatase , Calcitriol , Calcium , Dialysis , Ergocalciferols , Hyperparathyroidism, Secondary , Injections, Intraperitoneal , Kidney Failure, Chronic , Korea , Parathyroid Hormone , Parathyroidectomy , Peritoneal Dialysis, Continuous Ambulatory , Renal DialysisABSTRACT
Recombinant AAV serotype 8 (rAAV8) vector is new and promising for gene delivery,which transduces muscular and hepatic cells highly efficiently. The transduction varies with the administration routes. It was observed that the rAAV8 virus injected intraperitoneally had been delivered to many different tissues through the blood circulation and resulted in extensive and prolonged gene expression. The interest gene (human coagulation factor Ⅸ) has been highly expressed via the rAAV8 vector injected intraperitoneally into mice at the dose of 5?1010 gc/ mouse. Considerable expression was detected in mouse plasma at two weeks after the administration. Expression peak up to 1 000% level compared to the UCRP occurred between 1~2 months after administration, and then the expression declined gradually but obvious expression persisted at 4 months post administration. APTT test proved the clotting activity of the recombinant hFⅨ in mouse plasma. Immunohistochemical assay showed that the human coagulation factor has been expressed significantly in several organs including liver, kidney, heart and muscles (abdominal and hindleg). These suggest that the rAAV8 virus injected intraperitoneally has been delivered via blood circulation and transduced different cells of multi-organs, and the product of the gene mediated by the rAAV8 vector is biologically active.
ABSTRACT
A 30-minutes infusion of "tungog" in normal saline was injected intraperitoneally to 59 white Sprague rats. Marked clinical and anatomic changes developed in animals which received 10 to 20 serial injections of 0.5 cc of the infusion 1 to 2 times a week plus a single additional dose of 0.75 cc per 100-gram body weight. The liver and spleen were contracted and deformed in more than 50% of the subjects. The hepatic cells showed varying degrees of hyaline and feathery degeneration which sometimes proceeded to necrosis. Concomitantly, there was secondary regenerating hyperplasia often to a marked degree. The changes in the spleen were described. (Author)