ABSTRACT
Objective Analysis of the effect and the mechanism of adenovirus with down regulation of matrix metalloproteinase inhibitor 1 (TIMP-1) achieved targeting by ultrasound microbubbles combined with ultrasound irradiation for liver fibrosis in rats. Methods Recombinant adenovirus-mediated with down regulation of TIMP-1 gene was constructed and a mixture of recombinant adenovirus and ultrasound contrast agent was prepared.The rat liver fibrosis model was established and divided into 5 groups : model group; adenovirus group (recombinant adenovirus); adenovirus microbubble group (mixture of recombinant adenovirus and ultrasound contrast agent); experimental group (ultrasound irradiation + mixture of recombinant adenovirus and ultrasound contrast agent); ultrasound adenovirus group (ultrasound irradiation + recombinant adenovirus). The rats were sacrificed after 24 hours and liver sections were prepared. The expression of EGFP in each group was observed and the transfection rate was analyzed. The liver slices were stained by Masson to judge the stage of liver fibrosis. ANOVA analysis was used to compare the levels of alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , bydroxyproline (Hyp) , hyaluronic acid (HA) , type IV collagen (CIV) and laminin (LN) in each group. The relative expression levels of TIMP-1 and matrix metalloproteinase 13 (MMP-13) in each group were detected by Western blot. Results The transfection rate of the experimental group was higher than that of the adenovirus group (q = 3.418) , the adenovirus microbubble group (q = 3.756) and the ultrasonic adenovirus group (q = 5.502) , and the difference was statistically significant (P < 0.05); Pathological examination showed that the degree of fibrosis in the experimental group and the grade of liver fibrosis were lower than the other groups (P < 0.01). The activities of ALT, AST, HA, LN, CIV and Hyp in the experimental group were lower than those in the other 4 groups.Western blot showed that the level of TIMP-1 protein expression was highest while the level of MMP-13 protein expression was lowest in the experimental group than those in the other groups. Conclusion Adenovirus with down regulation of TIMP-1 achieved targeting by ultrasound microbubbles combined with ultrasound irradiation can inhibit the activity of TIMP-1 and improve the degree of liver fibrosis. Gene therapy is an potential therapeutic method in the application of treating liver fibrosis.
ABSTRACT
Objective: To investigate the effects of artesunate (ART) on diabetic retinopathy of rats by detecting the expression variation of matrixmetalloproteinase-9 (MMP-9) and inhibitory factor matrix metalloproteinase inhibitor-1 (TIMP-1) in retina. Methods: A total of 24 healthy male SD rats were randomly divided into negative control, model control and ART treated groups. The model control group and ART treated group were given injection of streptozotocin (STZ) to establish the type 1 diabetic rat model. After being raised for three months, the ART treated rats' abdomina were given ART injection for 10 d. All retinas of three groups were isolated. The expression of MMP-9 and TIMP-1 mRNA was detected by Real-time PCR (RT-qPCR) and the expression of MMP-9 protein was detected by immunohistochemical staining. Results: The expression of MMP-9 in ART treated group was significantly decreased compared with model control group (P < 0.05), whereas TIMP-1 in ART treated group was significantly increased (P < 0.05). The immunohistochemical staining showed that the positive expression of MMP-9 protein in ART treated group was significantly less than that in model control group. Conclusion: ART has inhibitory effects on the expression of MMP-9 in the diabetic retinopathy of rats.
ABSTRACT
Objective:To investigate the curative efficacy of combined use of dexamethasone palmitate,vitamin B12 and lidocaine in the treatment of knee osteoarthritis and its effects on the seum levels of interleukin-1 (IL-1),matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-1 (TIMP-1).Methods:84 patients with osteoarthritis of knee were selected from August 2014 to July 2015 in Sixth Affiliated Hospital of Xinjiang Medical University and divided into the observation group and the control group according to the order of admission,42 cases in each group.The observation group was given intra-articular injection of dexamethasone palmitate,vitamin B12 and lidocaine,and the control group was treated with traditional Chinese medicine.The clinical efficacy was evaluated after treatment.The changes of serum IL-1,MMP-3,TIMP-1 levels and visual analogue (VAS) score were compared before and at 1 months after treatment.Results:After treatment,the total effective rate of observation group was significantly higher than that of the control group (P＜0.05),the serum levels ofIL-1,MMP-3 levels and VAS score were significantly lower than those before treatment,serum TIMP-1 level was obviously higher than that before treatment(P ＜0.05),the serum levels of IL-1,MMP-3 levels were significantly lower in the observation group than those of the control group,while the serum TIMP-1 level was obviously higher than(P＜0.05) Conclusion:Intra-articular injection with dexamethasone palmitate,vitamin B12 and lidocaine could effectively decrease the levels of serum IL-1 and MMP-3,increase the level ofTIMP-1,and relieve the pain in the patients with knee osteoarthritis.