| It has been nearly 60 years since the silicone gel breast implants had been applied in breast augmentation or reconstruction after mastectomy. Although the controversy on its safety never stopped, no sufficient evidence has ever proved it related to the occurrence of autoimmune disorders or breast cancer. Nevertheless, variable complications after breast implantation now and then happened, and the most frequent and severe one is adverse capsular contracture. Clinically, it causes hardness, pain, and even deformation of patients'breast, unilaterally or bilaterally, slightly bothering their daily life or severely leading to reoperation. Hence, it has become a hot spot in the plastic and reconstructive field, and lot of researches have been done in order to make clear its mechanism, but regretfully, it still remains unclear. Even though, current studies imply it highly pathologically similar to diseases characterized by excessive fibrosis: the fibroblasts overreact when provocated by some biological or chemical or physical stimulators, by proliferating activatedly, synthesizing and excreting massive extracellular matrix, and transforming into some contractile cell phenotype, myofibroblasts. Clinicians have dedicated in improving the operation technique, reforming the implants'filler as well as its shell, and developing different kind of drugs in order to lower the incidence of capsular contracture, however, no specially effective means has been found. Asiaticoside is one of three triterpenoid saponins derived from the Centalla asiatica, a Chinese traditional herb, and has been proved efficient in inhibitting the proliferation and synthesis of fibroblasts. Several dosage forms have been developed and applied in preventing and treating hypertrophic scars and kloids with prominent therapeutic effect and high safety. But no attempt has ever taken to extend its usage to prevent capsular contracture after breast implantation. Objective: To study the effect of asiaticoside in controlling capsule formation and to explore and investigate its possible mechanism, with a purpose to guide future clinical practice concerned on preventing capsular contracture after breast implantation. Methods: Forty female Sprague-Dawley rats were implanted with 2 silicone elastomer in hibateral dorsal interscapular region subcutaneously each, then were randomly assigned to 2 groups(n=20):Control group and Experiment group. The Experimental group was intragastric administrated with asiaticoside 24mg/Kg daily while the control group with saline of identical volume. On week1, 2, 4, 8 and 12, 4 rats from each group were sacrificed. Specimens were gathered for: 1. HE staining. Image-pro Plus was applied to measure the thickness of capsule at different time intervals and the dynamic alteration in histology was observed ; 2. Capsular collagen content assay , by means of L2Hprohydroxyproline determination; 3. Evaluating the expression of TGF-β1,α-SMA,PCNA in capsules 4, 8, 12 weeks after implantation respectvely with immunohistochemistry SABC method. Result: 1. 1 week after implantation, acute imflammation were observed in both group, and it diminished gradually; 4 weeks after implantation, typical capsule structure has developed in both group, and fibroblasts become the dominant cellular component in the capsule, distributed among the parallel lined collagen bundles; With the implantation duration prolonged, amount of fibroblasts in control group increased dramatically,and the capsule became dense and thick; Comparably ,the amount of fibroblasts in the experiment group is smaller and the capsule is looser and thinner. 2. The thickness of capsule in both group increased with implantation duration, but significant deviation appeared 4 weeks after operation, and it remained until 12 weeks later, when control group reached 306.08±31.31μm while only 194.33±23.27μm in the experiment group (P<0.05). 3. Collagen content in both group also increased with implantation duration, and similar to the capsular thickness develop tendency, significant deviation could be observed between the two groups 4 weeks after implantation, and it remained till the end of the experiment with 50.61±1.23mg/L in experiment group, 65.60±3.61 mg/L in control group (P<0.05) . 4. Immunohistochemical index in both group were obsvered 4, 8, 12 weeks after implantation. The staining intensity of TGF-β1 in both group decreased with the implantation duration increased; α-SMA positive cell rate varied slightly while PCNA positive cell ratio descend apparentely with the implant duration prolonging. But for all the three indexes, at any one of the three time intervals, significant deviation persists between the two groups(P<0.05). Conclusion: Asiaticoside can effectively inhibit the fibrosis procedure during the initial capsular formation around the silicone gel breast implant and reduce the capsular thickness in a rat model. Its mechanism may lies in 4 aspects as followed: 1. to inhibit theexpression of TGF-β1 in fibroblasts, or to depress whose downstreaming message transducting molecules, and consequently decrease the deposition of extracellular matrix;2. to inhibit the proliferation of fibroblasts derectly;3. to depress the expression of α-SMA through down regulating the expression of TGF-β1. It can possibly helpful in preventing capsular contracture after breast implantation in clinic.
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