Based on Wnt/β-Catenin Signal Pathway to Explore the Mechanism of Tongluotangtai Recipe on GK Rats with Diabetes Peripheral Neuropathy / 世界科学技术-中医药现代化

Objective Exploring the effect of Tong luo tang tai(TLTT)on diabetic peripheral neuropathy(DPN)in GK rats with Wnt/β-The influence of the catenin signaling pathway.Methods Fifty GK rats were randomly divided into model group,TLTT high,medium,and low dose groups,and Western medicine group,with 10 rats in each group.Another 10 wistar rats were selected as the normal group.Except for the normal group,all other groups were fed with high fat to prepare DPN rat models.After 15 weeks,the DPN model was successfully prepared,and the rats in each group were treated by gavage.The high,medium,and low dose groups of TLTT were given traditional Chinese medicine TLTT 28 g·kg-1,14 g·kg-1,and 7 g·kg-1,respectively.The western medicine group was given metformin 100 mg·kg-1 and mecobalamin 0.2 mg·kg-1 by gavage.Rats in each group were administered once a day for 8 consecutive weeks.The general state,fasting blood sugar(FBS),thermal contraction latency(TWL),motor nerve conduction velocity(MNCV),and pathological changes in the sciatic nerve tissue were observed under transmission electron microscopy(Real time PCR)Western blot detection of wingless MMTV integration site family member 3A(Wnt3a)β Catenin(β-Catenin,Glycogen Synthesis Kinase-3β Glycogen synthesis kinase-3β,GSK-3β)MRNA and protein expression levels of antagonists(WNT inhibitor factor-1,Wif-1)on the Wnt signaling pathway.Results Compared with the normal group,the model group showed poorer general condition and significant pathological ultrastructural changes in the sciatic nerve.Its FBS level increased(P<0.01),TWL level decreased(P<0.01),and MNCV significantly slowed down(P<0.01).The model group had Wnt3a β-Catenin,GSK-3β MRNA and protein expression levels decreased(P<0.05),while Wif-1 mRNA and protein expression levels increased(P<0.01).After drug intervention,compared with the model group,the general condition and pathological ultrastructure of the sciatic nerve were improved in the TLTT high,medium,low,dose,and Western medicine groups,with a decrease in FBS levels(P<0.01)and an increase in TWL levels(P<0.05).The MNCV of each TLTT dose group and Western medicine group was significantly improved(P<0.01).The Wnt3amRNA of the TLTT high-dose group and Western medicine group was significantly increased(P<0.05),while the Wif-1mRNA of the TLTT high-dose group and Western medicine group was significantly reduced(P<0.05),There was a significant increase in Wnt3 protein in the high-dose and Western medicine groups of TLTT(P<0.01),as well as in the high-dose,medium,and low-dose TLTT and western medicine groups β-Catenin protein significantly increased(P<0.01,P<0.05),with high,medium,and low doses of TLTT and Western medicine group GSK-3β The protein significantly increased(P<0.01,P<0.05),while the Wif-1 protein significantly decreased(P<0.01,P<0.05)in the high and medium dose TTLTT and western medicine groups.Conclusion Tongluo Tangtai can alleviate sciatic nerve injury in DPN to a certain extent,and its mechanism may be related to the activation of Wnt/β,the catenin signaling pathway is involved.

A short review on the features of the non-obese diabetic Goto-Kakizaki rat intestine

The Goto-Kakizaki (GK) rat is a non-obese experimental model of type 2 diabetes mellitus (T2DM) that allows researchers to monitor diabetes-induced changes without jeopardizing the effects of obesity. This rat strain exhibits notable gastrointestinal features associated with T2DM, such as marked alterations in intestinal morphology, reduced intestinal motility, slow transit, and modified microbiota compared to Wistar rats. The primary treatments for diabetic patients include administration of hypoglycemic agents and insulin, and lifestyle changes. Emerging procedures, including alternative therapies, metabolic surgeries, and modulation of the intestinal microbiota composition, have been shown to improve the diabetic state of GK rats. This review describes the morpho-physiological diabetic-associated features of the gastrointestinal tract (GIT) of GK rats. We also describe promising strategies, e.g., metabolic surgery and modulation of gut microbiota composition, used to target the GIT of this animal model to improve the diabetic state.

Analysis of Excretion Behavior of GK-A from Ginkgo Semen in Urine and Bile of Rats / 中国实验方剂学杂志

Objective::To investigate excretion of GK-A, a antitussive compound separated from Ginkgo Semen, in the urine and bile of rats. Method::UPLC-MS/MS was used to determine the concentration of GK-A in rat urine and bile samples. The separation was performed on a C18 column, the mobile phase consisted of 0.1%formic acid aqueous solution (A) and acetonitrile (B) for gradient elution (0-1 min, 95%A; 1-3 min, 95%-85%A; 3-7.5 min, 85%-40%A; 7.5-8 min, 40%A). The detection was carried out by a triple quadrupole mass spectrometer in the positive ion mode with an electrospray ionization (ESI). Multiple reaction monitoring (MRM) mode was employed. After intragastric administration of GK-A, the urine and bile samples were collected at different time points, and the contents of GK-A in the samples were determined, and the cumulative excretion and cumulative excretion rate were calculated. Result::After 72 h of administration, the cumulative excretion of GK-A in urine was (12.35±2.69) μg, and the cumulative excretion rate was (0.58±0.13)%. Meanwhile, after 24 h of administration, the cumulative excretion of GK-A in bile was (55.16±29.22) μg, and the cumulative excretion rate was (1.57±0.83)%. Only a small amount of GK-A was excreted from urine and bile of rats with a slow speed. Conclusion::After intragastric administration, the excretion of GK-A in rat urine and bile is not the main elimination pathway.

Mechanism of Danzhi Jiangtang Capsules in treatment of diabetic macrovascular disease in GK rats based on correlation between microRNAs and inflammatory factors / 中国中药杂志

This study was aimed to investigate the mechanism of Danzhi Jiangtang Capsules( DJC) in the treatment of diabetic macrovascular disease in Goto-Kakizaki( GK) rats. The diabetic macrovascular disease rat model was induced by feeding high-fat and high-sugar combined with endothelial nitric oxide synthase( NOS) inhibitor N-nitro-L-arginine methyl ester( L-NAME)( 0. 1 g·L-1·d-1). According to the random array table,the model rats were randomly divided into the model group,DJC groups( 1 260,630,320 mg·kg-1),atorvastatin group( 105 mg·kg-1) and metformin group( 10 mg·kg-1),with 12 rats in each group. The rats received gavage administration for 8 weeks. Twelve Wistar rats were selected as the normal control group. The changes of body weight,water intake,blood glucose,plasma total cholesterol( TC),triglyceride( TG),high density lipoprotein( HDL-C),low density lipoprotein( LDL-C),interleukin( IL-1β),IL-6,tumor necrosis factor( TNF-α),nitric oxide( NO),endothelin( ET-1) were observed in these rats. Aortic tissue was taken and the pathological changes were observed by HE staining. RT-PCR was used to detect the mRNA levels of IL-1β,IL-6,and TNF-α in rat aorta. RT-PCR of the stem loop was used to detect the levels of miRNA-126,miRNA-155,miRNA-146 a,and miRNA-21 in rat plasma and aortic tissue. The canonical correlation between miRNAs and inflammatory factors was then analyzed. The results showed that DJC increased the rat body weight,lowered water intake,reduced the random blood glucose,reversed the rat aorta tissue damage,reduced serum TC,TG,LDL-C,ET-1,IL-1β,IL-6,TNF-α,as well as miRNA-155,miRNA-146 a and miRNA-21 levels in serum,elevated plasma HDL-C,NO content,reduced the aorta mRNA of IL-1β,IL-6,TNF-α,and the miRNA-155,miRNA-146 a and miRNA-21,elevated miRNA-126 expression in aorta. Aortic miRNA-126,miRNA-155,miRNA-146 a and miRNA-21 expression levels were typically correlated with the expression of inflammatory factors,among which miRNA-126 was negatively correlated,miRNA-155,miRNA-146 a and miRNA-21 were positively correlated with the factors. These results suggested that DJC had therapeutic effects on diabetic macrovascular diseases,and the mechanism of action may be related to the regulation of miRNA-126,miRNA-155,miRNA-146 a and miRNA-21 levels,as well as the reduction of inflammatory factors and vascular inflammatory response.

Protective effect of Yiqi Huoxue decoction on kidney in diabetic GK rats / 中国中药杂志

To investigate the protective effect of Yiqi Huoxue decoction on the kidney in diabetic goto-Kaizaki (GK) rats. Eight Wistar rats were used as normal control group. According to body weight and blood glucose, 16 GK rats were randomly divided into model control group and Yiqi Huoxue group, with 8 rats in each group. Drugs were administrated for 6 weeks. The rats were weighed and fasting blood glucose (FBG) were measured weekly; the glycosylated hemoglobin (HbALc) and 24 h metabolic rate were measured at the end of third and sixth weeks, at the same time, urine was collected to measure urinary glucose (U-GLU), urinary creatinine (U-CREA) and total proteinuria (U-TP) by biochemical method and calculate 24 h protein excretion rate (UAER). At the end of treatment, rats were sacrificed in anesthesia, and creatinin (CREA), uric acid (UA) and cholesterol (CHOL) were detected by biochemical method and glutathione peroxidase (GSH-Px) was detected by manual method with the blood drawn from heart. Both kidneys were taken and weighed to calculate the renal hypertrophy index. The kidneys were placed into neutral formalin and observed under light microscope for pathological change after Periodic Acid-Schiff (PAS) staining. The results showed that as compared with the normal control group, FBG, HbALc, 24 h Metabolic rate, U-GLU, UAER, serum CREA, UA and CHOL levels, as well as renal hypertrophy index were significantly increased (<0.05) in the model group, while the body weight growth rate, serum GSH-Px level were significantly reduced(<0.05); in addition, renal glomerular injury and structural changes were observed in the model group. As compared with the model group, serum GSH-Px level was significantly increased (<0.05) in the Yiqi Huoxue group, While FBG, HbALc, 24 h Metabolic rate, U-GLU, UAER, serum CREA, UA and CHOL levels, as well as renal hypertrophy index were significantly reduced (<0.05); meanwhile, renal glomerular injury and structural changes were improved in the Yiqi Huoxue group. The results showed that Yiqi Huoxue decoction can significantly increase serum GSH-Px level, reduce FBG, HbALc, 24 h metabolic rate, U-GLU, UAER, serum CREA, UA and CHOL levels, as well as renal hypertrophy index, and improve renal pathology in diabetic GK rats.

Improving effects of Huangdi Anxiao Capsules on insulin resistance in type 2 diabetic GK rats / 中成药

AIM To observe the effects of Huangdi Anxiao Capsules (Puerariae lobatae Radix,Eriobotryae Folium,Notoginseng Radix et Rhizoma,etc.) on blood glucose and insulin resistance in GK rats with type 2 diabetes mellitus (T2DM) and its possible mechanism of action.METHODS GK rats with T2DM included in the experiment were randomly divided into model group,rosiglitazone (1.44 mg/kg) group,Shenqi Jiangtang Granules (1.08 g/kg) group,Huangdi Anxiao Capsules high,medium and low (12,6,3 g/kg) group and normal control group of Wistar rats.After six weeks of consecutive administration,fasting blood glucose (FBG),serum insulin (FINS),fasting plasma glucose (FPG),and insulin resistance index (HOMA-IR) were measured in all groups.Serum biochemical indexes of (TG,TC,HDL-C,LDL-C),glycosylated hemoglobin (HbA1c),glucagon-like peptide (GLP-1) and insulin-like growth factor (IGF-1) were measured.The pancreatic tissue was obtained by routine paraffin embedding and HE staining to observe the pathological changes.RESULTS Compared with the normal group,FBG,FPG,FINS,HOMA-IR,TG,TC,HDL-C,LDL-C and HbA1c of the model group were significantly higher (P ＜0.01),and GLP-1 and IGF-1 expressions were markedly decreased (P ＜ 0.01).Compared with the model group,the levels of FBG,FPG,FINS,HOMA-IR,TG,TC,HDL-C,LDL-C and HbA1 c in Huangdi Anxiao Capsules high-,medium-and low-dose group were significantly decreased (P ＜ 0.05,P ＜0.01);GLP-1 and IGF-1 expressions were markedly increased (P ＜0.05,P ＜0.01),compared with the model group,the structure changes of pancreatic tissue in Huangdi Anxiao Capsules high-,medium-and low-dose groups largely reduced.CONCLUSION Huangdi Anxiao Capsules can reduce GK rats fasting blood glucose,insulin resistance,and its mechanism may be related to promoting the emergence and proliferation of pancreatic islet cells,improving the function of islet beta cells,and increasing insulin secretion.

Effect of modified gastric bypass on glycometabolism of non-obese type 2 diabetes mellitus in GK rats / 重庆医学

Objective To verify the feasibility and effectiveness of modified gastric bypass surgery in the treatment of non-obese type 2 diabetic mellitus(T2DM ) GK rats .Methods Forty male GK rats were randomly divided into four groups (n=10) ,the group A served as the modified gastric bypass ,group B as the Roux-en-Y gastric bypass ,group C as the sham operation and group D as the blank control group .Fasting blood glucose(FBG) ,glycosylated hemoglobin(HbA1c) and fasting serum insulin(FINS) in each group were detected at preoperative 1 week ,postoperative 1 ,2 ,4 ,8 ,12 weeks .Results The rat body mass at postoperative 1 week in the group A and B was significantly decreased compared with the group D ,and began to recover at postoperative 4 weeks , the rat body mass at the same time point had no statistical difference between the group A and B (P>0 .05) .FPG ,FINS and HbA1c at preoperative 1 week had no statistical difference among various groups (P>0 .05) .FPG and FINS at postoperative 1 week had no statistical difference among various groups (P>0 .05) .FPG and FINS at postoperative 2 ,4 ,8 ,12 weeks had no statistical difference between the group A and B(P>0 .05) ,which had no statistical difference between the group A with the group C and D (P>0 .05) . HbA1c at postoperative 4 weeks had no statistical difference among various groups (P>0 .05);which at postoperative 12 weeks had no statistical difference between the group A and B (P>0 .05) ,while which had no statistical difference between the group A with the group C and D(P>0 .05) .Conclusion The modified gastric bypass surgery has the improvement effect on glycometabolism of rat non-obese T2DM ,which is similar to that of Roux-en-Y gastric bypass surgery .

Pathological observation of two huge spontaneous tumors in a Wistar and a GK rats / 中国比较医学杂志

Objective To study the pathological features of two huge spontaneous tumors in Wistar and GK rats. Methods Forty Wistar rats and 40 GK rats were included in this study. Among those rats, two huge spontaneous tumors were observed in a Wistar rat at 14 months of age and in a GK rat at 22 months of age. The growth and survival status of the tumor?bearing rats were recorded. The tumors were surgically removed, and their pathological features were examined using HE and immunohistochemical staining (vimentin, CK19, α?SMA, CD31, CD34, S?100, NF及Ki?67). Results Both the two tumors were completely resected by surgery without much difficulties, and both host rats survived well after the operation. The weight of the two huge tumors was 502 g and 119 g, which corresponding to 64% and 24% of the body weight of their host rats, respectively. The tumors surface had a complete capsule, with a clear boundary separating from the normal surrounding tissues, and no vascular pedicle structure was found. According to the results of immunohistochemical staining, both the two tumors were diagnosed as benign fibroma. Conclusion This type of huge spontaneous tumors is benign fibroma. Besides the impact on the activities of the rats, the tumors have no significant impact on the living conditions in the hosts.

Effect of Huangqi-Wumei granule on insulin resistance in GK rats / 解放军医学杂志

Objective To observe the effect of Huangqi-Wumei (Mongolian milkvetch-Smoked plum, HW) granule on insulin resistance in GK rats. Methods Thirty-two male 4-week-old GK rats were randomly divided into four groups (8 each): model group, positive control group (metformin hydrochloride enteric-coated tablets, 0.15g/kg), low dose HW granule group (HW granule 1.3g/kg) and high dose HW granule group (HW granule 5.2g/kg); meantime 8 male Wistar rats of eight-week-old were used as normal control group (normal saline). During 10 weeks of gavage, multiple measurements of rats’ body weight and fasting blood glucose (FBG) were detected respectively on the 0, 2, 4, 6, 8 and 10 week. Fasting serum insulin (FINS) and glycosylated hemoglobin (GHb) were measured and insulin resistance index (HOMA-IR) was calculated at the end of the 10th week. Rats were sacrificed by acute blood loss, and the expressions of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) protein in rats’ liver were measured by Western blotting. Results Ten weeks after intervention, compared with the normal control group, no significant difference of the body weight existed in model group (P>0.05) and positive control group (P>0.05), but the body weight in HW granule groups reduced significantly (P<0.05). Compared with the normal control group, the FBG, GHb and HOMA-IR in the model group was significantly increased (P<0.05); compared with the model group, the HOMA-IR in HW granule groups and positive control group decreased significantly (P<0.05), the FINS and GHb in the high dose HW granule group and the positive control group decreased (P<0.05). Compared with the normal control group, the expression of IR and IRS-1 protein in the model group decreased (P<0.05). Compared with the model group, the expression of IR and IRS-1 protein in the HW granule groupsand the control group increased significantly (P<0.05). Conclusions HW granule may reduce the blood glucose, lose weight and attenuate insulin resistance of GK rats. The mechanism may be related to the increased expression of IR and IRS-1 protein in liver tissue of GK rats.

Renal blood perfusion in GK rats using targeted contrast enhanced ultrasonography

Objective:To explore application of targeted contrast enhanced ultrasonography in diagnosis of early stage vascular endothelial injury and diabetic nephropathy.Methods:Targeted SonoVue-TM microbubble was prepared by attaching anti-TM monoclonal antibody to the surface of ordinary micro-bubble SonoVue by biotin-avidin bridge method and ultrasonic instrument was used to evaluate the developing situation of targeted microbubble in vitro. Twenty 12-week-old male GK rats and 20 Wistar rats were enrolled in this study, and were randomly divided into targeted angiography group and ordinary angiography group. Targeted microbubbles SonoVue-TM or general microbubble SonoVue were rapidly injected to the rats via tail vein; the developing situation of the two contrast agents in rats kidneys was dynamically observed. Time intensity curve was used to analyse rat kidney perfusion characteristics in different groups. Results:Targeted ultrasound microbubble SonoVue-TM was successfully constructed, and it could be used to develop an external image. Targeted microbubbles SonoVue-TM enabled clear development of experimental rat kidney. Time intensity curve shapes of rat kidney of the two groups showed as single apex with steep ascending and slowly descending branch. Compared with the control group, the rising slope of the GK rat renal cortex, medulla in targeted angiography group increased(P<0.05); the peak intensity of medulla increased (P<0.05), and the total area under the curve of medulla increased (P<0.05). Compared with control group, the ascending branch of the GK rat in renal cortex, medulla in ordinary angiography group increased (P<0.05). The peak intensity of the curve increased (P<0.05), and the total area under the curve increased (P<0.05). Compared with the ordinary angiography group, the peak of GK rat medullacurve in targeted angiography group intensity increased (P<0.05), and the total area under the curve increased (P<0.05).Conclusions:Targeted microbubbles SonoVue-TM can make a clear development of experimental rat kidney, its stable performance meet the requirement of ultrasonic observation time limit, and it can reflect early changes of blood perfusion in GK rat kindey.

Glucolipid metabolism and antioxidant effect of the total flavones of propolis in GK rats / 中国药学杂志

OBJECTIVE: To study on glucolipid metabolism effect of the total flavones of propolis (TFP) in Goto-Kakisaki rats (GK Rats). METHODS: Fifty GK rats were randomly divided into 5 groups by blood glucose, the model group, positive drug group (2 000 mg · kg-1) and the high (240 mg · kg-1) dose of the TFP group, the medium (120 mg · kg-1) doses of the TFP group, low (60 mg · kg-1) doses of the TFP group. The GK rats in TFP groups were given with TFP by intragastric administration, continuously treated for 8 weeks, the control group were given equal sodium carboxymethylcellulose(CMC-Na) and positive drug group were given (2 000 mg · kg-1) dose of Xiaoke pills by intragastric administration. The glucose (Glu), total cholesterol (TC), triglyceride (TG), high density lipoprotein(HDL-C), low density lipoprotein(LDL-C), glycated hemoglobin(GHb), superoxide dismutase (SOD), ma-londialdehyde(MDA), glutathione(GSH), serum insulin(lNS), C-peptide(C-P), tumor necrosis factor-α(TNF-α) free fatty acid (FFA), nitric oxide(NO), and hepatic glycogen were measured at the end of the experiment. RESULTS: Compared with the control group, the levels of GLU, TG, TC, LDL-C, GHb, MDA and TNF-α were decreased significantly (P 0.05) in the low-dose group. The levels of SOD, hepatic glycogen, NO and C-P were increased significantly(P < 0.05 or P < 0.01), the levels of GLU, MDA, TG and GHb were decreased significantly (P < 0.05 or P < 0.01 or P < 0.001) in Xiaoke pills group. CONCLUSION: TFP can significantly decrease the level of blood glucose, significantly improve the glucose and lipid metabolism and inhibit insulin resistance in deficiency of GK rats.

Renal blood perfusion in GK rats using targeted contrast enhanced ultrasonography

OBJECTIVE@#To explore application of targeted contrast enhanced ultrasonography in diagnosis of early stage vascular endothelial injury and diabetic nephropathy.@*METHODS@#Targeted SonoVue-TM microbubble was prepared by attaching anti-TM monoclonal antibody to the surface of ordinary microbubble SonoVue by biotin - avidin bridge method and ultrasonic instrument was used to evaluate the developing situation of targeted microbubble in vitro. Twenty 12-week-old male GK rats and 20 Wistar rats were enrolled in this study, and were randomly divided into targeted angiography group and ordinary angiography group. Targeted microbubbles SonoVue-TM or general microbubble SonoVue were rapidly injected to the rats via tail vein; the developing situation of the two contrast agents in rats kidneys was dynamically observed. Time-intensity curve was used to analyze rat kidney perfusion characteristics in different groups.@*RESULTS@#Targeted ultrasound microbubble SonoVue-TM was successfully constructed, and it could be used to develop an external image. Targeted microbubbles SonoVue-TM enabled clear development of experimental rat kidney. Time-intensity curve shapes of rat kidney of the two groups showed as single apex with steep ascending and slowly descending branch. Compared with the control group, the rising slope of the GK rat renal cortex, medulla in targeted angiography group increased (P < 0.05); the peak intensity of medulla increased (P < 0.05), and the total area under the curve of medulla increased (P < 0.05). Compared with control group, the ascending branch of the GK rat in renal cortex, medulla in ordinary angiography group increased (P < 0.05). The peak intensity of the curve increased (P < 0.05), and the total area under the curve increased (P < 0.05). Compared with the ordinary angiography group, the peak of GK rat medulla curve in targeted angiography group intensity increased (P < 0.05), and the total area under the curve increased (P < 0.05).@*CONCLUSIONS@#Targeted microbubbles SonoVue-TM can make a clear development of experimental rat kidney, its stable performance meet the requirement of ultrasonic observation time limit, and it can reflect early changes of blood perfusion in GK rat kindey.

Renal blood perfusion in GK rats using targeted contrast enhanced ultrasonography

Objective: To explore application of targeted contrast enhanced ultrasonography in diagnosis of early stage vascular endothelial injury and diabetic nephropathy. Methods: Targeted SonoVue-TM microbubble was prepared by attaching anti-TM monoclonal antibody to the surface of ordinary microbubble SonoVue by biotin - avidin bridge method and ultrasonic instrument was used to evaluate the developing situation of targeted microbubble in vitro. Twenty 12-week-old male GK rats and 20 Wistar rats were enrolled in this study, and were randomly divided into targeted angiography group and ordinary angiography group. Targeted microbubbles SonoVue-TM or general microbubble SonoVue were rapidly injected to the rats via tail vein; the developing situation of the two contrast agents in rats kidneys was dynamically observed. Time-intensity curve was used to analyze rat kidney perfusion characteristics in different groups. Results: Targeted ultrasound microbubble SonoVue-TM was successfully constructed, and it could be used to develop an external image. Targeted microbubbles SonoVue-TM enabled clear development of experimental rat kidney. Time-intensity curve shapes of rat kidney of the two groups showed as single apex with steep ascending and slowly descending branch. Compared with the control group, the rising slope of the GK rat renal cortex, medulla in targeted angiography group increased (P < 0.05); the peak intensity of medulla increased (P < 0.05), and the total area under the curve of medulla increased (P < 0.05). Compared with control group, the ascending branch of the GK rat in renal cortex, medulla in ordinary angiography group increased (P < 0.05). The peak intensity of the curve increased (P < 0.05), and the total area under the curve increased (P < 0.05). Compared with the ordinary angiography group, the peak of GK rat medulla curve in targeted angiography group intensity increased (P < 0.05), and the total area under the curve increased (P < 0.05). Conclusions: Targeted microbubbles SonoVue-TM can make a clear development of experimental rat kidney, its stable performance meet the requirement of ultrasonic observation time limit, and it can reflect early changes of blood perfusion in GK rat kindey.

Asiatic acid mitigates hyperglycemia and reduces islet fibrosis in Goto-Kakizaki rat, a spontaneous type 2 diabetic animal model / 中国天然药物

The Goto-Kakizaki (GK) rat is a spontaneous type 2 diabetic animal model, which is characterized by a progressive loss of beta islet cells with fibrosis. In the present study, the hypoglycemic effect of asiatic acid (AA) in GK rats was examined. GK rats receiving AA at a daily dose of 25 mg·kg(-1) for four weeks showed a significant reduction in blood glucose levels. Age-matched normal Wistar rats were given 0.5% sodium carboxymethyl cellulose (CMC-Na) solution for the same periods and used as control. Compared to the normal Wistar rats, GK rats treated with AA showed improvement in insulin resistance partially through decreasing glucose level (P < 0.01) and insulin level (P < 0.05). Furthermore, the results of immunohistochemistry indicate that AA treatment reduced islet fibrosis in GK rats. Fibronectin, a key protein related to islet fibrosis, was over-expressed in GK rats, which was reversed significantly by AA treatment (P < 0.05). These findings suggest that AA has a beneficial effect on lowering blood glucose levels in GK rats and improves fibrosis of islets in diabetes, which may play a role in the prevention of islets dysfunction.

Observe the effectiveness of ileal transposition for weight and blood glucose / 国际外科学杂志

Objective Through developing the experimental animal model of ileal transposition (IT) with GK-rats,to explore the effects of ileal transposition on water and food intake,weight change and blood glucose.Methods Thirty male GK-rats were randomly assigned to three groups:IT(n =10),C (n =10) and B (n =10)group.Rats in IT group underwent ileal transposition,and others underwent sham operation.Every group was given sufficient clean water.Water and food intake,weight change blood glucose and oral glucose tolerance test(OGTT) were recorded preoperatively and postoperatively.Results The total deaths of the experiment was four and the general survival rate was 88.6％.After operation,water intake reduced visibly in all groups,IT group was kept low level for a long time but not in C and B group.The food intake of IT group was lower than the other two groups during a certain period,but that phenomenon didnt last long.The weight change showed similarly to the food intake.The fasting plasma glucose(FPG) and OGTT were ameliorated significantly in IT group but not in B and C group.Conclusions It is feasible to develop ileal transposition animal models with GK-rats.Moreover,the author found that the influence of IT on weight in GK rats was transient,but on water intake and blood glucose was lasting.

Exercise training and selenium or a combined treatment ameliorates aberrant expression of glucose and lactate metabolic proteins in skeletal muscle in a rodent model of diabetes

Exercise training (ET) and selenium (SEL) were evaluated either individually or in combination (COMBI) for their effects on expression of glucose (AMPK, PGC-1alpha, GLUT-4) and lactate metabolic proteins (LDH, MCT-1, MCT-4, COX-IV) in heart and skeletal muscles in a rodent model (Goto-Kakisaki, GK) of diabetes. Forty GK rats either remained sedentary (SED), performed ET, received SEL, (5 micromol/kg body wt(-1)/day(-1)) or underwent both ET and SEL treatment for 6 wk. ET alone, SEL alone, or COMBI resulted in a significant lowering of lactate, glucose, and insulin levels as well as a reduction in HOMA-IR and AUC for glucose relative to SED. Additionally, ET alone, SEL alone, or COMBI increased glycogen content and citrate synthase (CS) activities in liver and muscles. However, their effects on glycogen content and CS activity were tissue-specific. In particular, ET alone, SEL alone, or COMBI induced upregulation of glucose (AMPK, PGC-1alpha, GLUT-4) and lactate (LDH, MCT-1, MCT-4, COX-IV) metabolic proteins relative to SED. However, their effects on glucose and lactate metabolic proteins also appeared to be tissue-specific. It seemed that glucose and lactate metabolic protein expression was not further enhanced with COMBI compared to that of ET alone or SEL alone. These data suggest that ET alone or SEL alone or COMBI represent a practical strategy for ameliorating aberrant expression of glucose and lactate metabolic proteins in diabetic GK rats.

Influence of TangNaiKang on VEGF protein expression of GK rats thoracic aorta / 国际中医中药杂志

Objective To investigated the effect of TangNaiKang (TNK) on VEGF protein expression of GK rats Thoracic aorta. Methods 51 male GK rats were divided into five groups randomly: model group, pioglitazone group, and TNK treatment group (low, immediate and high dose). Another 10 male Wistar rats were served as normal control group. GK rats were fed with high-grease forage, while normal control group was fed with a standard diet. Fasting blood glucose, general HE staining and VEGF protein expression were detected by immunohistochemistry. Results The fasting glucose had a significant decline in TNK treatment groups. HE staining showing TNK can ameliorate intima thickness, reduce hyperplasia of shallow vascular smooth muscle cell, and improve wavy and plexiform arrangement of elastic lamina. Immunohistochemistry also showed that TNK decreased VEGF protein expression of great vessels. Conclusion TangNaiKang can prevent and cure diabetic vascular complication of GK rats.

A Case of Hyperacute Liver Failure from Mushroom Intoxication in a Child Treated with Penicillin / 대한소아소화기영양학회지

Hyperacute liver failure from mushroom intoxication in children is rare and has a low survival rate. We report a case of hyperacute liver failure from mushroom intoxication in a 29-month-old boy. The patient ingested a mushroom about three days prior to presentation. He was admitted to the hospital with vomiting, abdominal pain, seizures, and hematemesis. During the hospitalization the patient developed hepatic encephalopathy (stage IV-a), and a coagulopathy. He recovered fully with specific medication, Penicillin GK and N-acetylcysteine.

A Case of Hyperacute Liver Failure from Mushroom Intoxication in a Child Treated with Penicillin / 대한소아소화기영양학회지

Hyperacute liver failure from mushroom intoxication in children is rare and has a low survival rate. We report a case of hyperacute liver failure from mushroom intoxication in a 29-month-old boy. The patient ingested a mushroom about three days prior to presentation. He was admitted to the hospital with vomiting, abdominal pain, seizures, and hematemesis. During the hospitalization the patient developed hepatic encephalopathy (stage IV-a), and a coagulopathy. He recovered fully with specific medication, Penicillin GK and N-acetylcysteine.

Genome Mapping of an Extreme Thermophile, Thermus caldophilus GK24

Genome of an extreme thermophile, Thermus caldophilus GK24 has been analyzed to construct the genomic map. The genomic DNAs encapsulated in agarose gel were digested with SspI, EcoRI, SpeI, and HpaI restriction endonucleases, and then the resulting genomic DNA fragments were analyzed by pulsed-field gel electrophoresis. Its restriction map has been constructed by analyzing sizes of the restriction fragments obtained from both complete and partial digestions. The circular form of its genome was composed of about 1.98 Mbp and a megaplasmid. The genomic loci for the genes of xylose isomerase, thioredoxin, tRNA-16S rRNA, 23S rRNA, L5 ribosomal protein, ADP-glucose pyrophosphorylase, DNA-ligase, and Tca DNA polymerase were determined by both Southern hybridization and PCR.