| Background and ObjectiveDiabetic gastroparesis is a common gastrointestinal complications ofdiabetes. Our previous study have found: exogenous stem cell factor(SCF)through improvement or reversal interstitial cells of Cajal to improve partof gastric motility in diabetic gastroparesis rats,but the phenomenon ofgastric electrical-mechanical uncoupling was found in diabeticgastroparesis rats,which suggest the gastric antrum smooth muscle may beabnormal in itself, but the mechanism is not clear. RhoA/ROCK signalpathway is a Ca2+-dependent regulation of smooth muscle contractionmechanism,which is related to abnormal contraction of vascular smoothmuscle, bladder smooth muscle and uterine smooth muscle.WhetherRhoA/ROCK signal pathway is related to the pathogenesis of DGP, is notclear. The aim of our study is to investigate that whether exogenous stemcell factor improve gastric motility relating to RhoA/ROCK signalpathway.Methods1.30SD Rats were randomly divided into control group,diabetic mellitus(DM)group.DM group were intraperitoneally injected withstreptozotocin(STZ) at dosage of50mg/Kg,combined with high sugar highfat diet regularly,while rats in control group was injected with equivalentphosphate buffer solution(pH=7.4) and fed with standard diet.2.Ten weeks later, DM group were randomly divided into DGPgroup(n=9) and DGP+SCF group(n=9).DGP+SCF group wereintraperitoneally injected exogenous SCF0.4μg/(Kg·d) for20days, and thecontrol group and DGP group were given equivalent phosphate buffersolution(pH=7.4)for20days.3.Two days after the intervention, gastric emptying time was detectedby gastric residual pigment rate; expression of mRNA and protein of RhoAin gastric antrum smooth muscle tissue were detected byRT-PCR,immunohistochemistry and Western blot. Expression of mRNAand protein of ROCK1and ROCK2in gastric antrum smooth muscle tissuewere detected by RT-PCR,immunohistochemistry.Results1. We build DGP rat model Sucessfully; gastric emptying time wassignificantly higher in DGP group than that in control group（52.53%±4.38%vs38.57%±2.39%, P <0.05）, gastric emptying time wassignificantly lower in DGP+SCF group than that in DGP group（45.77%±3.89%vs52.53%±4.38%, P <0.05）.2. Expression of mRNA of RhoA was significantly lower in DGP group than that in control group （0.511±0.128vs0.979±0.150, P <0.05）,expression of mRNA of RhoA was significantly higher in DGP+SCF groupthan that in DGP group（0.780±0.164vs0.511±0.128, P <0.05）.3. Expression of protein of RhoA in immunohistochemistry wassignificantly lower in DGP group than that in control group（0.0819±0.0377vs0.2020±0.0428, P<0.05）, expression of protein of RhoA wassignificantly higher in DGP+SCF group than that in DGP group（0.1098±0.0434vs0.0819±0.0377, P <0.05）;expression of protein ofRhoA in Western blot was significantly lower in DGP group than that incontrol group （0.676±0.186vs1.084±0.103, P<0.05）, expression ofprotein of RhoA was significantly higher in DGP+SCF group than that inDGP group（0.905±0.167vs0.676±0.186, P<0.05）.4. Expression of mRNA of ROCK1and ROCK2was significantlylower in DGP group than that in control group （0.724±0.098vs0.975±0.110, P<0.05;0.234±0.067vs0.773±0.161, P<0.05）；expression ofmRNA of ROCK1and ROCK2was significantly higher in DGP+SCFgroup than those in DGP group（0.906±0.123vs0.724±0.098, P<0.05;0.463±0.086vs0.234±0.067, P<0.05）.5.Expression of protein of ROCK1and ROCK2inimmunohistochemistry was significantly lower in DGP group than those incontrol group（0.1021±0.0321vs0.4321±0.0446, P<0.05;0.2037±0.0367vs0.3672±0.0421, P<0.05）；expression of protein of ROCK1and ROCK2 was significantly higher in DGP+SCF group than those in DGP group（0.2456±0.037vs0.1021±0.0321,P<0.05;0.2923±0.0431vs0.2037±0.0367,P<0.05）.Conclusions1.Gastric emptying time in DGP rats was significantlydelayed,exogenous stem cell factor can significantly improve the gastricemptying.2.Down-regulation of RhoA/ROCK signal pathway is related to thepathogensis of DGP.3. Exogenous SCF can up-regulate RhoA/ROCK signal pathway ofgastric antrum smooth muscle in DGP rats. |
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