基于PI3K/Akt通路探讨宫粘2号方对宫腔粘连大鼠的影响OA

Objective It is to observe the effect of Gongzhan No.2 formula on endometrial and glandular injury in rats with uterine adhesions,and to explore its mechanism of action based on the phosphoinositide 3-kinase(PI3K)/protein ki-nase B(Akt)signaling pathway.Methods Sixty SPF grade female SD rats were taken,10 of which were randomly selected as sham operation group,and the 50 remaining rats were prepared with mechanical curettage and lipopolysaccharide infec-tion to establish models of uterine adhesions.The successfully modeled rats were randomly divided into model group,west-ern medicine group,the low-dose,medium-dose and high-dose groups of Gongzhan No.2 formula,with 9 rats in each group.The low-dose,medium-dose and high-dose groups of Gongzhan No.2 formula were administered decoctions of Gongzhan No.2 formula via gavage at concentrations of 0.675 g/mL,1.35 g/mL,and 2.7 g/mL,respectively,the western medicine group was administered a solution of estradiol valerate tablets at a concentration of 0.018 g/mL via gavage,while the sham opera-tion group and model group were administered normal saline via gavage.The administration volume was 10 mL/(kg·d)in each group,once daily,continuously treated for 21 days.The rats were dissected,and the appearance of their uterus was examined with naked eyes,the histopathological morphology of uterine tissue was observed by HE staining,the thickness of endometrium and the number of glands were measured,the protein expressions of CXC chemokine ligand 5(CXCL5),PI3K,Akt,and matrix metalloproteinase-9(MMP-9)in uterine tissue were detected by Western blot.Results Compared with the sham operation group,the uterus of rats in the model group exhibited multiple areas of visible narrowing,localized fluid accumulation and distension,a slightly darker color,a stiff texture,and poor elasticity;HE staining revealed that there were endometrial adhesions,extensive inflammatory cell infiltration,and fibrotic hyperplasia in uterus;furthermore,the endometrial thickness and the number of glands were significantly reduced(all P<0.05),the relative protein expres-sions of CXCL5 and MMP-9 in the uterine tissue were both significantly decreased(both P<0.05),while the relative pro-tein expressions of PI3K and Akt were both significantly increased(both P<0.05).Compared with the control group,the uterus of rats in the drug-treated groups was ruddy in appearance,soft in texture with good elasticity;the uterine cavity was more patent,with reduced inflammatory cell infiltration and tissue fibrosis,and the endometrial thickness and the number of glands were significantly increased(both P<0.05);the relative protein expressions of CXCL5 and MMP-9 in uterine tis-sue were significantly increased,while the relative protein expressions of PI3K and Akt were significantly reduced(all P<0.05).Compared with the western medicine group and low-dose group of Gongzhan No.2 formula,the improvements of en-dometrial thickness,gland count,and the relative protein expressions of CXCL5,MMP-9,PI3K and Akt in uterine tissue were more significant in the medium-dose and high-dose groups of Gongzhan No.2 formula(all P<0.05).Conclusion Gongzhan No.2 formula can alleviate endometrium and glands injury in rats with uterine adhesions,its mechanism of action may be related to up-regulating CXCL5 expression and inhibiting the PI3K/Akt signaling pathway,thereby up-regulating MMP-9 expression.