摘要
目的：探讨川芎嗪、环丙沙星对增殖性玻璃体视网膜病变（PVR）的影响及其机制，以评价临床应用防治PVR的可能性。
方法：
1、用胰蛋白酶消化法取材人结膜成纤维细胞，并描述人结膜成纤维细胞的生物学特性。
2、采用MTT法评价川芎嗪和环丙沙星对人结膜成纤维细胞增殖的抑制作用，显微镜观察细胞的形态学变化。
3、18只新西兰白兔随机分为6组，每只白兔左眼为对照眼，右眼玻璃体腔注射川芎嗪或环丙沙星。通过裂隙灯和直接检眼镜观察眼部情况。注药后24h处死白兔并快速摘除眼球，行眼组织学光学显微镜观察。
4、新西兰大白兔50只随机分5组。玻璃体腔注药后第4天重复注射相同剂量药物。第1、3、7、14、21、28天用裂隙灯、检眼镜观察并记录玻璃体视网膜改变，并眼底照相。
结果：
1、人结膜成纤维细胞的指数生长期为从接种后24h到第7天，
第7天后为平台期。
2、川芎嗪、环丙沙星对人结膜成纤维细胞增殖的抑制作用呈剂量依赖性，药物作用48h的半数抑制量（IC50值）分别为1.36mg/ml 、12.77ug/ml。
3、药物兔眼毒性评价中，环丙沙星12mg组视网膜有空泡样变性；其余各组未发现有毒性反应。
4、药物对PVR的作用实验中，注药后14天，各组兔眼玻璃体出现大小不等的纤维增生条索。术后28天，对照组增生条索增大，而各实验组增生条索减少。
结论：
1、川芎嗪、环丙沙星对人结膜成纤维细胞的增殖具有明显抑制作用；
2、光学显微镜检查显示，川芎嗪8mg或环丙沙星3mg玻璃体腔注射对兔眼无毒性作用,环丙沙星12mg对兔眼有毒性作用。
3、川芎嗪和环丙沙星能有效抑制PVR的发生、发展，可望为临床药物防治PVR提供新的途径。
4、其安全剂量范围、最佳的给药方式等有待进一步探讨
Purpose:To study the influence of Tetramethylpyrazine (TMP) and Ciprofloxacin on the proliferative vitreoretinopathy(PVR) and their mechanism, then to estimate the possibility of clinical application for provention and cure PVR.
Method:
1. To culture human conjunctiva fibroblast cells by trypsin digestion method and describe their growth features in vitro.
2. the function of TMP and Ciprofloxacin on the cell proliferative activity was evaluated by MTT method. Cell morphology was observed under the inverted light microscopy.
3. 18 New Zealand white rabbits were put into three groups randomly. The left eyes of each rabbit were control group.The right eyes each of the 18 rabbits received an intravitreal injection of Tetramethylpyrazine or Ciprofloxacin. The eyes were evaluated clinically
by means of slit-lamp examination and direct ophthalmoscopy before and after the intravitreal injection. The rabbits were killed after 24hs for light microscopic histopathologic analysis.
4. 50 rabbits were divided into 5 groups randomly.repeat to inject the same deal dosage medicine into the rabbit`s vitreous body After surgery 3 days. The fundus was examined immediately and was checked for hemorrhages or surgically induced detachments. Slit lamp biomicroscopy and direct ophthalmoscopy were repeated and recorded at 1、3、7、14、21 and 28 days after the blood injection.
Results:
1. The index number growth period of the human`s conjunctiva fibroblast cells is from after inoculating 24 hs to the 7th day, and the 7th day is platform period.
2. The cultured conjunctiva fibroblast cells proliferation was significantly inhibited by TMP and Ciprofloxacin. And the effect were dose dependent. The IC50 values of TMP and Ciprofloxacin on conjunctiva fibroblast cells on 48hs were 1.36mg/ml and 12.77ug/ml respectively.
3. After an intravitreal injection of TMP or Ciprofloxacin, there were bubble-like degeneration in these rabbits retinas in the 12mg Ciprofloxacin group. No evidence of toxic effects based on the clinical examinations and light microscopic examination in the others groups was
observed.
4. After 14 days, the vitreous bodies were changed from gray-red into brown-yellow, and present the widespread and yellow sediment-like turbid. Fiber strands in different size in the vitreous bodies appear in all groups. After 28 days, the proliferative fiber strands became thicker than before in control group and have more strands, while the fiber stands became thinner than before in others groups and have less fiber strands.
Conclusions:
1.TMP and Ciprofloxacin inhibit the proliferation of human conjunctiva fibroblast cells in a dose dependent manner .
2. A single intravitreal injection of TMP 8mg/0.4ml or Ciprofloxacin 3mg/0.1ml was nontoxic to rabbit ocular structures, as demonstrated by light microscopic examination. A intravitreal injection of ciprofloxacin 12mg/0.4ml had poison to rabbit ocular structures.
3. Intravitreal injiction of TMP and Ciprofloxacin can inhibit experimental PVR. TMP or Ciprofloxacin are potential to become adjunctive drugs as an addition to vitreoretinal surgery.
4.It should be further studied in the medicin`s safe dosage scope、best administer method and so on
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