硫辛酸对奥硝唑所致少弱精子症大鼠精子发生的保护作用研究

Lipoic acid protects spermatogenesis in male rats with ornidazole-induced oligoasthenozoospermia

目的:研究硫辛酸(LA)对奥硝唑(ORN)所致少弱精子症模型雄性大鼠生精功能的保护作用。方法:取70只雄性SD大鼠,随机分成7组,每组10只,分别为:A组(溶剂对照组):1 ml 0.5%羧甲基纤维素钠(CMC-Na)+1 ml橄榄油;B组(低剂量ORN造模组):400 mg/kg ORN+1 ml橄榄油;C组(低剂量ORN+低剂量LA治疗组):400 mg/kg ORN+50 mg/kg LA;D组(低剂量ORN+高剂量LA治疗组):400 mg/kg ORN+100 mg/kg LA;E组(高剂量ORN造模组):800 mg/kg ORN+1 ml橄榄油;F组(高剂量ORN+低剂量LA治疗组):800 mg/kg ORN+50 mg/kg LA;G组(高剂量ORN+高剂量LA治疗组):800 mg/kg ORN+100 mg/kg LA。连续给药20 d,处死大鼠,称量大鼠体重、睾丸、附睾、精囊重量,计算脏器指数,检测附睾精子计数及活力,睾丸、附睾做HE染色观察组织形态学改变。结果:与A组相比,E组大鼠体重增量、睾丸、附睾脏器指数明显减少[(117.67±11.53)g vs(88.11±12.65)g;(1.06±0.12)%vs(0.65±0.13)%;(0.21±0.03)%vs(0.17±0.01)%,P均<0.01];与E组相比,F组大鼠附睾脏器指数明显增加[(0.17±0.01)%vs(0.20±0.02)%,P<0.01],G组大鼠体重增量、睾丸、附睾脏器指数明显增加[(88.11±12.65)g vs(102.70±16.10)g,P<0.05;(0.65±0.13)%vs(0.95±0.06)%,P<0.01;(0.17±0.01)%vs(0.19±0.02)%,P<0.05],精囊脏器指数各组之间并无明显差异。与A组相比,B组大鼠精子活力明显降低[(74.12±8.73)%vs(40.25±6.08)%,P<0.01],E组大鼠精子计数与活力明显降低[(38.59±6.40)×105/100 mg vs(18.67±4.59)×105/100 mg;(74.12±8.73)%vs(27.58±8.43)%,P均<0.01];与B组相比,C、D组大鼠精子活力明显增加[(40.25±6.08)%vs(58.13±7.62)%;(40.25±6.08)%vs(76.04±8.44)%,P均<0.01];与E组相比,F、G组大鼠精子计数及活力明显增加[(18.67±4.59)×10~5/100 mg vs(25.63±9.66)×10~5/100 mg,P<0.05;(18.67±4.59)×10~5/100 mg vs(29.92±4.15)×10~5/100 mg,P<0.01;(27.58±8.43)%vs(36.56±11.08)%,P<0.05;(27.58±8.43)%vs(45.05±9.59)%,P<0.01]。A、B、C、D组大鼠睾丸、附睾组织形态学无明显改变。E组大鼠睾丸与A组相比,生精小管腔内可见坏死脱落的生精细胞,生精细胞层次不清,排列紊乱;附睾管腔中精子数目明显减少,并伴有较多非细胞成分存在。F、G组大鼠睾丸生精小管内精子数目增加,但仍可见到生精小管内有生精细胞脱落,生精细胞层次不清晰,排列紊乱,但较E组有明显改善;F、G组大鼠附睾管腔中精子数目明显减少,可见散在、脱落的生精细胞,但较E组有明显改善。结论:LA能够改善ORN对大鼠造成的生殖系统损伤,提高精子质量,对生殖系统有较好的保护作用。

Objective： To study the protective effect of lipoic acid （LA） on the spermatogenic function of the male rats with oligoasthenozoospermia induced by ornidazole （ORN）. Methods： Seventy male SD rats were equally randomized into groups A （sol- vent control： 1 ml 0.5% CMC-Na ± 1 ml olive oil）, B （low-dose ORN model： 400 mg/kg ORN suspension ± 1 ml olive oil）, C （low-dose ORN ± low-dose LA treatment： 400 mg/kg ORN ± 50 mg/kg LA）, D （low-dose ORN ± high-dose LA treatment： 400 mg/kg ORN ± 100 mg/kg LA）, E （high-dose ORN model： 800 mg/kg ORN suspension ± 1 ml olive oil）, F （high-dose ORN ± low-dose LA treatment： 800 mg/kg ORN ± 50 mg/kg LA）, and G （high-dose ORN ± high-dose LA treatment： 800 mg/kg ORN ± 100 mg/kg LA）, and treated respectively for 20 successive days. Then all the rats were sacrificed and the weights of the body, tes- tis, epididymis and seminal vesicle obtained, followed by calculation of the organ index, determination of epididymal sperm concentra- tion and motility, and observation of the histomorphological changes in the testis and epididymis by HE staining. Results ： Compared with group A, group E showed significantly decreased body weight （ [ 117.67 ± 11.53 ] vs [ 88.11 ± 12.65 ] g, P 〈 0.01 ） and in- dexes of the testis （[1.06 ± 0.12] vs [0.65 ± 0.13] %, P 〈 0.01） and epididymis （[0.21 ± 0.03] vs [0.17 ± 0.01] %, P 〈 0.01 ）. In comparison with group E, group F exhibited remarkable increases in the epididymal index （ [0.17 ± 0.01 ] vs [0.20 ± 0.02] %, P 〈 0.01）, and so did group G in the body weight （[88.11 ± 12.65] vs [102.70 ± 16.10] g, P 〈 0.05） and the indexes of the testis （[0.65 ± 0.13] vs [0.95±0.06] %, P 〈 0.01） and epididymis （[0.17 ± 0.01] vs [0.19 ± 0.02] % , P 〈 0.05）, but no obvious difference was observed in the index of seminal vesicle among different groups. Compared with group A, group B manifested significant decreases in sperm motility （ [74.12 ± 8.73] vs [40.25 ± 6.08] %, P 〈 0.01）, and so did group E in sperm count （[38.59± 6.40] vs [18.67 ± 4.59] xl0S/100mg, P 〈 0.01） and sperm motility （[74.12 ± 8.73] vs [27.58 ± 8.43] %, P 〈 0.01）. Sperm motility was significantly lower in group B than in C and D （[40.25 ± 6.08] vs [58.13 ± 7.62] and [76.04 ± 8.44]%, P 〈 0.01）, and so were sperm count and motility in group E than in F and G （ [18.67 ± 4.59] vs [25.63 ± 9.66] and [29.92 ± 4.15] ×10^5/100 mg, P 〈 0.05 andP 〈 0.01; [27.58 ± 8.43] vs [36.56 ± 11.08 ] and [45.05±9.59] %, P 〈 0.05 and P 〈 0.01 ）. There were no obvious changes in the histomorphology of the testis and epididymis in groups A, B, C and D. Compared with group A, group E showed necrotic and exfoliated spermatogenic cells with unclear layers and disorderly arrangement in the seminiferous tubules and remarkably reduced sperm count with lots of noncellular components in the epididymal cavity, while groups F and G exhibited increased sperm count in the seminiferous tubules and epididymis lumen, also with exfoliation, unclear layers and disorderly arrangement of spermatogenic cells, but significantly better than in group E. Conclu- sion ： LA can reduce ORN-induced damage to the spermatogenetic function of rats, improve sperm quality, and protect the reproductive system.