DCI after Aneurysmal Subarachnoid Hemorrhage Is Related to the Expression of MFG-E8.

OBJECTIVE: To explore the predictive value of milk fat globule epidermal growth factor 8 (MFG-E8) in the occurrence of delayed cerebral ischemia (DCI) after an aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We recruited 32 patients with aSAH as the case group and 24 patients with unruptured aneurysms as the control group. Serum MFG-E8 levels were measured by western blot and enzyme-linked immunosorbent assay. We analyzed the relationship between MFG-E8 levels and the risk of DCI. RESULTS: The levels of serum MFG-E8 in the case group (mean = 11160.9 pg/mL) were significantly higher than those in the control group (mean = 3081.0 pg/mL, p < 0.001). MFG-E8 levels highly correlated with the World Federation of Neurosurgical Societies (WFNS) and modified Fisher scores (r = -0.691 and - 0.767, respectively, p < 0.001). In addition, MFG-E8 levels in patients with DCI (5882.7 ± 3162.4 pg/mL) were notably higher than those in patients without DCI (15818.2 ± 3771.6 pg/mL, p < 0.001). A receiver operating characteristic curve showed that the occurrence of DCI could effectively be predicted by MFG-E8 (area under the curve = 0.976, 95%CI = 0.850-1.000). Kaplan-Meier survival analysis showed a remarkable decrease in the incidence of DCI in case group individuals with high levels of MFG-E8 (≥11160.9 pg/mL, p < 0.001). CONCLUSION: MFG-E8 may be a useful predictive marker for DCI after an aSAH and could be a promising surrogate end point.

[Shenjing Guben Pills for repairing testicular spermatogenic injury induced by oxidative stress in rats].

OBJECTIVE: To investigate the antioxidative and spermatogenesis-repairing effects of Shenjing Guben Pills (SGP), a Chinese medicine for invigorating the kidney and blood circulation, on the testis, epididymis and sperm in rats with oxidative stress injury (OSI) induced by cadmium chloride. METHODS: Seventy-two male Wistar rats were equally randomized into six groups: normal control, OSI model control, Wuzi Yanzong Pills (WYP) and low-, medium- and high-dose SGP. The OSI model was made in the latter five groups by intraperitoneal injection of cadmium chloride at 1 mg/kg, and 24 hours later, the rats of the normal and model control groups treated intragastrically with 0.9% normal saline, those of the WYP group with WYP at 4.5 g/kg/d, and those of the low-, medium- and high-dose SGP groups with SGP at 2.8, 5.6 and 11.2 g/kg/d, respectively, all for 56 days. Then, all the animals were sacrificed for obtainment of the visceral indexes and histopathological changes of the testis, epididymis and seminal vesicle, measurement of sperm concentration and motility and the percentage of morphologically normal sperm (MNS) in the epididymis, and determination of the levels of glutathione perox-idase (GSH-PX), superoxide dismutase (SOD), malondial-dehyde aldehyde (MDA) and serum testosterone (T). RESULTS: Compared with the OSI model controls, the rats in the high-, medium- and low-dose SGP groups showed significantly higher visceral indexes of the testis (ï¼»0.237 ± 0.098ï¼½ vs ï¼»0.403 ± 0.090ï¼½, ï¼»0.357 ± 0.150ï¼½ and ï¼»0.348 ± 0.140ï¼½ g/100 g, P < 0.05) and seminal vesicle (ï¼»0.241 ± 0.118ï¼½ vs ï¼»0.347 ± 0.115ï¼½, ï¼»0.336 ± 0.090ï¼½ and ï¼»0.320 ± 0.065ï¼½ g/100 g, P < 0.05) and those of the high-dose SGP group in the epididymal index (ï¼»0.099 ± 0.088ï¼½ vs ï¼»0.156 ± 0.030ï¼½ g/100 g, P < 0.05). In comparison with the OSI model controls, the animals of the high-, medium- and low-dose SGP groups exhibited significant increases in sperm concentration (ï¼»10.5 ± 17.7ï¼½ vs ï¼»58.1 ± 32.2ï¼½, ï¼»36.0 ± 36.2ï¼½ and ï¼»31.9 ± 32.7ï¼½ ×106/ml, P < 0.05) and serum T (ï¼»2.56 ± 0.75ï¼½ vs ï¼»3.62 ± 0.96ï¼½, ï¼»3.48 ± 1.33ï¼½ and ï¼»3.24 ± 0.83ï¼½ nmol/L, P < 0.05 or P < 0.01), and those of the high- and medium-dose SCG groups in total sperm motility (ï¼»9.5 ± 13.0ï¼½% vs ï¼»26.5 ± 15.5ï¼½% and ï¼»18.9 ± 8.2ï¼½%, P < 0.05) and MNS (ï¼»36.2 ± 40.2ï¼½% vs ï¼»85.3 ± 23.3ï¼½% and ï¼»65.8 ± 28.1ï¼½%, P < 0.05) and the levels GSH-PX (ï¼»3.62 ± 2.22ï¼½ vs ï¼»5.70 ± 1.73ï¼½ and ï¼»5.42 ± 2.35ï¼½ U/mg prot, P < 0.05 ) and SOD (ï¼»41.3 ± 8.8ï¼½ vs ï¼»52.7 ± 14.6ï¼½ and ï¼»51.3 ± 14.7ï¼½ U/mg prot, P < 0.05). The MDA level, however, was markedly decreased in the high-, medium- and low-dose SGP groups (ï¼»0.41 ± 0.29ï¼½, ï¼»0.44 ± 0.19ï¼½ and ï¼»0.47 ± 0.20ï¼½ nmol/mg prot) as compared with that in the OSI model controls (ï¼»0.69 ± 0.28ï¼½ nmol/mg prot) (P < 0.05). Histopathological examinations manifested coagulative necrosis, calcification and disappearance of spermatogenic and Sertoli cells in the seminiferous tubules of the OSI model controls, with decreased intraluminal secretions and atrophic epithelial papillae in the seminal vesicles and non-sperm cells in the narrowed lumens of the atrophic epididymis. With the increased dose of SGP, the proportion of normal seminiferous tubules was enlarged, the epithelia of the seminal vesicle became column-shaped again, and the epididymal lumens grew lager with more sperm cells, which indicated a dose-dependent therapeutic efficacy. Medium- and high-dose SGP achieved a significantly better effect than WYP. CONCLUSIONS: Shenjing Guben Pills can antagonize oxidative stress, elevate the levels of testicular antioxidant enzymes and serum T, repair pathological injury of the testis, epididymis and seminal vesicle, and improve semen quality and spermatogenic function.