The Study Of The Treatment Effects By Combine Of Calpain Inhibitor And α-lipoic Acid In Experimental Cancer Cachexia

Objective: To investigate the treatment effects of calpain inhibitor and α-lipoic acidalone and their combination in mice with cancer cachexia and its possible mechanism.Methods: Forty male Balb/c mice were randomly divided into four groups:group A(healthy control group),group B (brearing cancer group),group C (ALLN group),group D (α-lipoic acid group), group E (ALLN+α-lipoic acid).The B,C,D and Egroups were subcutaneously inoculated cancer cells Colon26(C26), and then weregiven different drugs intervention for7days after cancer cachexia mode wassuccessfully established.The mice’s general state,body weight,food intake and tumorvolume were surveyed everyday.Non-tunor weight,gastrocnemius muscle weight,epididymis fat wet weight,the serum levels of blood biochemical indexes,cytokines,caplain-1and ubiqutin mRNA,and the activity of SOD were detected.Results:1. The tumor can be touched after the tumor cells were subcutaneously into the micefor4-5days.The body weights were significantly decreased to9day and the miceturned into cancer cachexia state.2. The initial body weights among all groups had not significant difference.After9days,the cancer cachexia modes were successfully established,the body weights incancer bearing group were significantly lower than that in group A(P<0.05).The finalweight,non-tumor weight,daily food intake,gastrocnemius muscle weight andepididymis fat wet weight were significantly decreased (P<0.01)3. Comparing with group A,the serum levels of total protein,albumin level and bloodglucose in tumor brearing was lower (P<0.05),and the TG level was higher(P<0.01).The levels of albumin and TG in group C,D and E were improved than thatin group B(P<0.01).The differences of blood glucose level among the tumor-brearingbrearing groups were not statistically significant (P>0.05). 4. The levels of TNF-α、IL-6and CRP increased comparing with the tumor bearinggroups(P<0.01), and that in C,D and E groups were significantly improved comparingcomparing with B group (P<0.01). The SOD level of all tumor bearing groupsdecreased (P<0.01), the MDA level increased (P<0.01). The SOD level in group Eimproved more significantly that in group C and D (P<0.05).5. The P65nuclear translocations were higher in group B (P<0.05),and the F-kBp65nuclear translocations expression level and cores decreased in group C,D and Ecomparing with group B (P<0.05).6. the Calpain-1and ubiquitin mRNA level in skeletal muscle of tumor bearing micedecreased (P<0.01). Calpain-1mRNA level in group E was lower than that in groupD (P<0.01), and the ubiquitin mRNA level was lower than that in group C and D(P<0.05).Conclusion:The mechanisms of Calpain inbitor ALLN and the strong antioxidant α-lipoicacid against cancer cachexia may be inhibiting the activation of calcium proteasomeway and improving the redox state. The combination of them have a better effect thanusing them alone.