Abstract:Objective To analyze the influence mechanism of macrophage inflammatory protein 1 α（MIP-1α）in bone destruction in mice by establishing the mouse model of multiple myeloma (MM). Methods Twenty-four non-obese diabetic/severe combined immunodeficiency (NOD/SCID) female mice were randomly divided into three groups: conventional modeling group, modeling inhibition group and blank control group ( n =8, each). Except for blank control group, the mice of other two groups were inoculated with RPMI 8226 cell suspension to establish MM mouse models. After successfully modeling, Y-27632 pathway inhibitor was injected subcutaneously in modeling inhibition group, and the same volume of normal saline was injected in other two groups for 1 week. At the end of the experiment, the mice in each group were subjected to immunohistochemistry, X-ray and the expression levels of MIP-1α, bone alkaline phosphatase(BALP), RhoA and ROCK1 to analyze the possible influence mechanism of MIP-1α on the bone destruction of MM model mice. Results There were 6 cases of lower limb paralysis (75.00%) in conventional modeling group and 4 cases of lower limb paralysis (50.00%) in modeling inhibition group. Compared with blank control group, malignant plasma cells, increased osteoclasts, serious bone destruction and surrounding soft tissue swelling appeared obviously in the visual field of pathological slices in conventional modeling group. However, there were decreased osteoclast number, with slightly damaged bone and slightly swollen soft tissue shadow around tibia bone in inhibition modeling group. The expression levels of MIP-1α in conventional modeling group [(332.80±85.60) pg/ml] and in inhibition modeling group [(296.40±67.54) pg/ml] were significantly higher than that [(8.40±2.36) pg/ml] in blank control group ( P <0.01). Compared with those in blank control group, BALP level decreased, and RhoA and ROCK1 levels increased in conventional modeling group ( P <0.05). However, in modeling inhibition group, MIP-1α expression decreased to some extent, BALP level increased, and the expression levels of RhoA and ROCK1 were significantly decreased because of pathway inhibitor Y-27632. Conclusions MIP-1α may play roles in bone destruction of MM model mice through the RhoA/ROCK1 signaling pathway. Therefore, inhibiting the expression of MIP-1α is of great significance for reducing bone destruction and prolonging the survival of MM mice.